<PAGE>

                                                                     EXHIBIT 4.5

THE SECURITIES EVIDENCED HEREBY HAVE NOT BEEN REGISTERED UNDER THE SECURITIES
ACT OF 1933, AS AMENDED OR ANY STATE SECURITIES LAWS. NO SALE OR DISPOSITION MAY
BE EFFECTED WITHOUT (i) EFFECTIVE REGISTRATION STATEMENTS RELATED THERETO, (ii)
AN OPINION OF COUNSEL OR OTHER EVIDENCE, REASONABLY SATISFACTORY TO THE COMPANY,
THAT SUCH REGISTRATIONS ARE NOT REQUIRED, (iii) RECEIPT OF NO-ACTION LETTERS
FROM THE APPROPRIATE GOVERNMENTAL AUTHORITIES, OR (iv) OTHERWISE COMPLYING WITH
THE PROVISIONS OF SECTION 7 OF THE AMENDED AND RESTATED WARRANT UNDER WHICH
THESE SECURITIES WERE ISSUED, DIRECTLY OR INDIRECTLY.

                            STRUCTURAL GENOMIX, INC.

                    AMENDED AND RESTATED WARRANT TO PURCHASE
                            SHARES OF PREFERRED STOCK

      THIS CERTIFIES THAT, for value received, SILICON VALLEY BANK and its
assignees are entitled to subscribe for and purchase that number of the fully
paid and nonassessable shares of Series Preferred (as defined below and as
adjusted pursuant to Section 4 hereof, the "Shares") of STRUCTURAL GENOMIX,
INC., a Delaware corporation (the "Company"), as is determined pursuant to the
next paragraph hereof at the price per share as is determined pursuant to the
next paragraph hereof (such price and such other price as shall result, from
time to time, from the adjustments specified in Section 4 hereof is herein
referred to as the "Warrant Price"), subject to the provisions and upon the
terms and conditions hereinafter set forth. As used herein, (a) the term "Series
Preferred" shall mean: (x) the Company's presently authorized Series C-1
Preferred Stock, or (y) in the event that immediately following a Qualified
Financing (as defined below) the initial Warrant Price is less than $8.45 (as
equitably adjusted for any stock split, recapitalization or the like affecting
the Company's presently authorized Series C-1 Preferred Stock), the same series
of convertible preferred stock as sold by the Company in its next Qualified
Financing, and, in either case, any stock into or for which such stock may
hereafter be converted or exchanged, and (z) after the automatic conversion of
the series preferred stock issuable hereunder to common stock, the Company's
Common Stock; (b) the term "Original Warrant Grant Date" shall mean July 15,
2002; and (c) the term "Other Warrants" shall mean any other warrants issued by
the Company in connection with the transaction with respect to which this
Amended and Restated Warrant was issued, and any warrant issued upon transfer or
partial exercise of or in lieu of this Amended and Restated Warrant. The term
"Amended and Restated Warrant" as used herein shall be deemed to include Other
Warrants unless the context clearly requires otherwise.

      The Warrant Price shall be the lower of (a) $8.45 (as equitably adjusted
for any stock split, recapitalization or the like affecting the Company's
presently authorized Series C1-Preferred Stock) and (b) the lowest effective
price per share (on a common stock equivalent basis and taking into account any
securities issued together with the preferred stock) at which shares of the
Company's convertible preferred stock are sold in a Qualified Financing;
provided that if a Qualified Financing has not closed prior to the exercise of
this Amended and Restated Warrant, then the Warrant Price shall be the price
determined pursuant to the preceding clause (a). A

<PAGE>

"Qualified Financing" shall mean the sale of the convertible preferred stock
(anticipated to be Series E1 Preferred Stock) of the Company to purchasers which
include venture capital investors in an aggregate cash amount not less than
$15,000,000. The number of shares for which this Amended and Restated Warrant is
exercisable shall be the nearest whole number determined by dividing $150,000 by
the Warrant Price determined pursuant to this paragraph.

      1. Term. The purchase right represented by this Amended and Restated
Warrant is exercisable, in whole or in part, at any time and from time to time
from the Original Warrant Grant Date through the later of (i) ten (10) years
after the Original Warrant Grant Date or (ii) five (5) years after the closing
of the Company's initial public offering of its Common Stock ("IPO") effected
pursuant to a Registration Statement on Form S-1 (or its successor) filed under
the Securities Act of 1933, as amended (the "Act").

      2. Method of Exercise; Payment; Issuance of New Amended and Restated
Warrant. Subject to Section 1 hereof, the purchase right represented by this
Amended and Restated Warrant may be exercised by the holder hereof, in whole or
in part and from time to time, at the election of the holder hereof, by (a) the
surrender of this Amended and Restated Warrant (with the notice of exercise
substantially in the form attached hereto as Exhibit A-1 duly completed and
executed) at the principal office of the Company and by the payment to the
Company, by certified or bank check, or by wire transfer to an account
designated by the Company (a "Wire Transfer") of an amount equal to the then
applicable Warrant Price multiplied by the number of Shares then being
purchased; (b) if in connection with a registered public offering (other than
the IPO) of the Company's securities in which securities of selling stockholders
(other than the Company) are registered, the surrender of this Amended and
Restated Warrant (with the notice of exercise form attached hereto as Exhibit
A-2 duly completed and executed) at the principal office of the Company together
with notice of arrangements reasonably satisfactory to the Company for payment
to the Company either by certified or bank check or by Wire Transfer from the
proceeds of the sale of shares to be sold by the holder in such public offering
of an amount equal to the then applicable Warrant Price per share multiplied by
the number of Shares then being purchased; or (c) exercise of the "net issuance"
right provided for in Section 10.2 hereof. The person or persons in whose
name(s) any certificate(s) representing shares of Series Preferred shall be
issuable upon exercise of this Amended and Restated Warrant shall be deemed to
have become the holder(s) of record of, and shall be treated for all purposes as
the record holder(s) of, the Shares represented thereby (and such Shares shall
be deemed to have been issued) immediately prior to the close of business on the
date or dates upon which this Amended and Restated Warrant is exercised. In the
event of any exercise of the rights represented by this Amended and Restated
Warrant, certificates for the Shares of stock so purchased shall be delivered to
the holder hereof as soon as possible and in any event within thirty (30) days
after such exercise and, unless this Amended and Restated Warrant has been fully
exercised or expired, a new Amended and Restated Warrant representing the
portion of the Shares, if any, with respect to which this Amended and Restated
Warrant shall not then have been exercised shall also be issued to the holder
hereof as soon as possible and in any event within such thirty-day period;
provided that at such time as the Company is subject to the reporting
requirements of the Securities Exchange Act of 1934, as amended, if requested by
the holder of this Amended and Restated Warrant, the Company shall cause its
transfer agent to deliver the certificate representing Shares issued upon
exercise of this Amended and Restated Warrant to a broker or other person (as
directed by the holder exercising this Amended and Restated Warrant) within the
time period required to settle any trade made by the holder after exercise of
this Amended and Restated Warrant.

                                      -2-
<PAGE>

      3. Stock Fully Paid; Reservation of Shares. All Shares that may be issued
upon the exercise of the rights represented by this Amended and Restated Warrant
will, upon issuance pursuant to the terms and conditions herein, be fully paid
and nonassessable, and free from all preemptive rights and taxes, liens and
charges with respect to the issue thereof. During the period within which the
rights represented by this Amended and Restated Warrant may be exercised, the
Company will at all times have authorized, and reserved for the purpose of the
issue upon exercise of the purchase rights evidenced by this Amended and
Restated Warrant, a sufficient number of shares of its Series Preferred to
provide for the exercise of the rights represented by this Amended and Restated
Warrant and a sufficient number of shares of its Common Stock to provide for the
conversion of the Series Preferred into Common Stock.

      4. Adjustment of Warrant Price and Number of Shares. The number and kind
of securities purchasable upon the exercise of this Amended and Restated Warrant
and the Warrant Price shall be subject to adjustment from time to time upon the
occurrence of certain events, as follows:

            (a) Reclassification or Merger. In case of any reclassification or
change of securities of the class issuable upon exercise of this Amended and
Restated Warrant (other than a change in par value, or from par value to no par
value, or from no par value to par value, or as a result of a subdivision or
combination), or in case of any merger of the Company with or into another
corporation (other than a merger with another corporation in which the Company
is the acquiring and the surviving corporation and which does not result in any
reclassification or change of outstanding securities issuable upon exercise of
this Amended and Restated Warrant), or in case of any sale of all or
substantially all of the assets of the Company, the Company, or such successor
or purchasing corporation, as the case may be, shall duly execute and deliver to
the holder of this Amended and Restated Warrant a new Amended and Restated
Warrant (in form and substance satisfactory to the holder of this Amended and
Restated Warrant), or the Company shall make appropriate provision without the
issuance of a new Amended and Restated Warrant, so that the holder of this
Amended and Restated Warrant shall have the right to receive upon exercise of
this Amended and Restated Warrant, at a total purchase price not to exceed that
payable upon the exercise of the unexercised portion of this Amended and
Restated Warrant, and in lieu of the shares of Series Preferred theretofore
issuable upon exercise of this Amended and Restated Warrant, the kind and amount
of shares of stock, other securities, assets and property receivable upon such
reclassification, change, merger or sale by a holder of the number of shares of
Series Preferred then purchasable under this Amended and Restated Warrant. Any
new Amended and Restated Warrant shall provide for adjustments that shall be as
nearly equivalent as may be practicable to the adjustments provided for in this
Section 4. The provisions of this Section 4(a) shall similarly apply to
successive reclassifications, changes, mergers and sales.

            (b) Subdivision or Combination of Shares. If the Company at any time
while this Amended and Restated Warrant remains outstanding and unexpired shall
subdivide or combine its outstanding shares of Series Preferred, the Warrant
Price shall be proportionately decreased and the number of Shares issuable
hereunder shall be proportionately increased in the case of a subdivision and
the Warrant Price shall be proportionately increased and the number of Shares
issuable hereunder shall be proportionately decreased in the case of a
combination;

                                      -3-
<PAGE>

provided that the holder of this Amended and Restated Warrant shall not be
entitled to any adjustment pursuant to this Section 4(b) that would duplicate
the effect of any adjustments effecting the Series Preferred made pursuant to
the Charter (as defined below).

            (c) Stock Dividends and Other Distributions. If the Company at any
time while this Amended and Restated Warrant is outstanding and unexpired shall
(x) pay a dividend with respect to Series Preferred payable in Series Preferred,
then the Warrant Price shall be adjusted, from and after the date of
determination of stockholders entitled to receive such dividend or distribution,
to that price determined by multiplying the Warrant Price in effect immediately
prior to such date of determination by a fraction (A) the numerator of which
shall be the total number of shares of Series Preferred outstanding immediately
prior to such dividend or distribution, and (B) the denominator of which shall
be the total number of shares of Series Preferred outstanding immediately after
such dividend or distribution; or (y) make any other distribution not covered
under the immediately preceding clause (x) with respect to Series Preferred
(except any distribution specifically provided for in Sections 4(a) and 4(b)),
then, in each such case, provision shall be made by the Company such that the
holder of this Amended and Restated Warrant shall receive upon exercise of this
Amended and Restated Warrant a proportionate share of any such dividend or
distribution as though it were the holder of the Series Preferred (or Common
Stock issuable upon conversion thereof) as of the record date fixed for the
determination of the stockholders of the Company entitled to receive such
dividend or distribution; provided that the holder of this Amended and Restated
Warrant shall not be entitled to any adjustment pursuant to this Section 4(c)
that would duplicate the effect of any adjustments effecting the Series
Preferred made pursuant to the Charter (as defined below).

            (d) Adjustment of Number of Shares. Upon each adjustment in the
Warrant Price pursuant to this Section 4, the number of Shares of Series
Preferred purchasable hereunder shall be adjusted, to the nearest whole share,
to the product obtained by multiplying the number of Shares purchasable
immediately prior to such adjustment in the Warrant Price by a fraction, the
numerator of which shall be the Warrant Price immediately prior to such
adjustment and the denominator of which shall be the Warrant Price immediately
thereafter.

            (e) Antidilution Rights. The other antidilution rights applicable to
the Shares of Series Preferred purchasable hereunder are set forth in the
Company's Certificate of Incorporation, as amended through September ___, 2004
(the "Amended and Restated Warrant Date"), a true and complete copy of which is
attached hereto as Exhibit B (the "Charter"). The Company shall promptly provide
the holder hereof with any restatement, amendment, modification or waiver of the
Charter promptly after the same has been made.

      5. Notice of Adjustments. Whenever the Warrant Price or the number of
Shares purchasable hereunder shall be adjusted pursuant to Section 4 hereof, the
Company shall make a certificate signed by its Chief Financial Officer or Vice
President of Finance setting forth, in reasonable detail, the event requiring
the adjustment, the amount of the adjustment, the method by which such
adjustment was calculated, and the Warrant Price and the number of Shares
purchasable hereunder after giving effect to such adjustment, and shall cause
copies of such certificate to be mailed (without regard to Section 13 hereof, by
first class mail, postage prepaid) to the holder of this Amended and Restated
Warrant. In addition, whenever the conversion price or conversion ratio of the
Series Preferred shall be adjusted, the Company shall make a certificate signed
by its Chief Financial Officer or Vice President of Finance setting forth, in

                                      -4-
<PAGE>

reasonable detail, the event requiring the adjustment, the amount of the
adjustment, the method by which such adjustment was calculated, and the
conversion price or ratio of the Series Preferred after giving effect to such
adjustment, and shall cause copies of such certificate to be mailed (without
regard to Section 13 hereof, by first class mail, postage prepaid) to the holder
of this Amended and Restated Warrant. Whenever the Warrant Price or the number
of Shares purchasable hereunder shall be adjusted pursuant to the occurrence of
a Qualified Financing, the Company shall make a certificate signed by its Chief
Financial Officer or Vice President of Finance setting forth, in reasonable
detail, the event requiring the adjustment, the amount of the adjustment, the
method by which such adjustment was calculated, and the Warrant Price and the
number of Shares purchasable hereunder after giving effect to such adjustment,
and shall cause copies of such certificate to be mailed (without regard to
Section 13 hereof, by first class mail, postage prepaid) to the holder of this
Amended and Restated Warrant.

      6. Fractional Shares. No fractional shares of Series Preferred will be
issued in connection with any exercise hereunder, but in lieu of such fractional
shares the Company shall make a cash payment therefor based on the fair market
value of the Series Preferred on the date of exercise as reasonably determined
in good faith by the Company's Board of Directors.

      7. Compliance with Act; Disposition of Amended and Restated Warrant or
Shares of Series Preferred.

            (a) Compliance with Act. The holder of this Amended and Restated
Warrant, by acceptance hereof, agrees that this Amended and Restated Warrant,
and the shares of Series Preferred to be issued upon exercise hereof and any
Common Stock issued upon conversion thereof are being acquired for investment
and that such holder will not offer, sell or otherwise dispose of this Amended
and Restated Warrant, or any shares of Series Preferred to be issued upon
exercise hereof or any Common Stock issued upon conversion thereof except under
circumstances which will not result in a violation of the Act or any applicable
state securities laws. Upon exercise of this Amended and Restated Warrant,
unless the Shares being acquired are registered under the Act and any applicable
state securities laws or an exemption from such registration is available, the
holder hereof shall confirm in writing that the shares of Series Preferred so
purchased (and any shares of Common Stock issued upon conversion thereof) are
being acquired for investment and not with a view toward distribution or resale
in violation of the Act and shall confirm such other matters related thereto as
may be reasonably requested by the Company. This Amended and Restated Warrant
and all shares of Series Preferred issued upon exercise of this Amended and
Restated Warrant and all shares of Common Stock issued upon conversion thereof
(unless registered under the Act and any applicable state securities laws) shall
be stamped or imprinted with a legend in substantially the following form:

"THE SECURITIES EVIDENCED HEREBY HAVE NOT BEEN REGISTERED UNDER THE SECURITIES
ACT OF 1933, AS AMENDED, OR ANY STATE SECURITIES LAWS. NO SALE OR DISPOSITION
MAY BE EFFECTED WITHOUT (i) EFFECTIVE REGISTRATION STATEMENTS RELATED THERETO,
(ii) AN OPINION OF COUNSEL OR OTHER EVIDENCE, REASONABLY SATISFACTORY TO THE
COMPANY, THAT SUCH REGISTRATIONS ARE NOT REQUIRED, (iii) RECEIPT OF NO-ACTION
LETTERS FROM THE APPROPRIATE GOVERNMENTAL AUTHORITIES, OR (iv) OTHERWISE
COMPLYING WITH THE PROVISIONS OF SECTION 7 OF THE AMENDED AND RESTATED WARRANT
UNDER WHICH THESE SECURITIES WERE ISSUED, DIRECTLY OR INDIRECTLY."

                                      -5-
<PAGE>

      Said legend shall be removed by the Company, upon the request of a holder,
at such time as the restrictions on the transfer of the applicable security
shall have terminated. In addition, in connection with the issuance of this
Amended and Restated Warrant, the holder specifically represents to the Company
by acceptance of this Amended and Restated Warrant as follows:

                  (1) The holder is aware of the Company's business affairs and
financial condition, and has acquired information about the Company sufficient
to reach an informed and knowledgeable decision to acquire this Amended and
Restated Warrant and the shares of Series Preferred issuable upon exercise
hereof and any Common Stock issuable upon conversion thereof. The holder is
acquiring this Amended and Restated Warrant and the shares of Series Preferred
issuable upon exercise hereof and any Common Stock issuable upon conversion
thereof for its own account for investment purposes only and not with a view to,
or for the resale in connection with, any "distribution" thereof in violation of
the Act.

                  (2) The holder understands that this Amended and Restated
Warrant and the shares of Series Preferred issuable upon exercise hereof and any
Common Stock issuable upon conversion thereof have not been registered under the
Act in reliance upon a specific exemption therefrom, which exemption depends
upon, among other things, the bona fide nature of the holder's investment intent
as expressed herein. The holder realizes that the basis for the exemption may
not be present if, notwithstanding its representations, the holder has a present
intention of acquiring the securities for a fixed or determinable period in the
future, selling (in connection with a distribution or otherwise), granting any
participation in, or otherwise distributing the securities. The holder has no
such present intention, other than potential transfers between affiliates

                  (3) The holder further understands that this Amended and
Restated Warrant and the shares of Series Preferred issuable upon exercise
hereof and any Common Stock issuable upon conversion thereof must be held
indefinitely unless subsequently registered under the Act and qualified under
any applicable state securities laws, or unless exemptions from registration and
qualification are otherwise available. The holder is aware of the provisions of
Rule 144, promulgated under the Act. The holder is further aware that certain
conditions for resale set forth in Rule 144 have not been satisfied and that the
Company presently has no plans to satisfy these conditions in the foreseeable
future.

                  (4) The holder is an "accredited investor" as such term is
defined in Rule 501 of Regulation D promulgated under the Act.

            (b) Disposition of Warrant or Shares. With respect to any offer,
sale or other disposition of this Amended and Restated Warrant or any shares of
Series Preferred acquired pursuant to the exercise of this Amended and Restated
Warrant or Common Stock issued upon conversion thereof prior to registration of
such Amended and Restated Warrant or shares, the holder hereof agrees to give
written notice to the Company prior thereto, describing briefly the manner
thereof, together with a written opinion of such holder's counsel, or other
evidence, if reasonably satisfactory to the Company, to the effect that such
offer, sale or other disposition may be effected without registration or
qualification (under the Act as then in effect or any federal or state
securities law then in effect) of this Amended and Restated Warrant or such

                                      -6-
<PAGE>

shares of Series Preferred or Common Stock and indicating whether or not under
the Act certificates for this Amended and Restated Warrant or such shares of
Series Preferred or Common Stock to be sold or otherwise disposed of require any
restrictive legend as to applicable restrictions on transferability in order to
ensure compliance with such law. Upon receiving such written notice and
reasonably satisfactory opinion or other evidence, the Company, as promptly as
practicable but no later than fifteen (15) days after receipt of the written
notice, shall notify such holder that such holder may sell or otherwise dispose
of this Amended and Restated Warrant or such shares of Series Preferred or
Common Stock, all in accordance with the terms of the notice delivered to the
Company. If a determination has been made pursuant to this Section 7(b) that the
opinion of counsel for the holder or other evidence is not reasonably
satisfactory to the Company, the Company shall so notify the holder promptly
with details thereof after such determination has been made. Notwithstanding the
foregoing, this Amended and Restated Warrant or such shares of Series Preferred
or Common Stock may, as to such federal laws, be offered, sold or otherwise
disposed of in accordance with Rule 144 or 144A under the Act; provided that the
Company shall have been furnished with such information as the Company may
reasonably request to provide a reasonable assurance that the provisions of Rule
144 or 144A have been satisfied. Each certificate representing this Amended and
Restated Warrant or the shares of Series Preferred or Common Stock thus
transferred (except a transfer pursuant to Rule 144 or 144A) shall bear a legend
as to the applicable restrictions on transferability in order to ensure
compliance with such laws, unless in the aforesaid opinion of counsel for the
holder, such legend is not required in order to ensure compliance with such
laws. The Company may issue stop transfer instructions to its transfer agent in
connection with such restrictions. Notwithstanding the foregoing, the holder
(including any transferee of the original holder) shall not transfer this
Amended and Restated Warrant or shares of Series Preferred or Common Stock to
any competitor of the Company, as determined in good faith by the Company's
Board of Directors.

            (c) Applicability of Restrictions. Neither any restrictions of any
legend described in this Amended and Restated Warrant nor the requirements of
Section 7(b) above shall apply to any transfer of, or grant of a security
interest in, this Amended and Restated Warrant (or the Series Preferred or
Common Stock obtainable upon exercise thereof) or any part hereof (i) to a
partner of the holder if the holder is a partnership or to a member of the
holder if the holder is a limited liability company, or (ii) to Silicon Valley
Bancshares (holder's parent company) or any affiliate of the holder if the
holder is a corporation or bank; provided that in any such transfer, (x) the
transferee shall agree in writing to be bound by the terms of this Amended and
Restated Warrant as if an original holder hereof, and (z) other than the
transfer to Silicon Valley Bancshares the transferor shall give the Company
prior written notice thereof in reasonable detail, including the name of the
transferee and the extent of the rights and/or number of shares to be
transferred. Subject to the provisions of this Section 7(c), upon receipt by
holder of the executed Amended and Restated Warrant, holder will transfer all or
part of this Amended and Restated Warrant or the Shares issuable upon exercise
of this Amended and Restated Warrant (or the securities issuable, directly or
indirectly, upon conversion of the Shares, if any) to Silicon Valley Bancshares,
holder's parent company. Subject to the provisions of this Section 7(c) and upon
providing Company with written notice and the transferee providing the Company
with transferee's agreement to be bound by the terms of this Amended and
Restated Warrant, holder or Silicon Valley Bancshares may transfer all or part
of this Amended and Restated Warrant or the Shares issuable upon exercise of
this Amended and Restated Warrant (or the securities issuable, directly or
indirectly, upon conversion of the Shares, if any) to The Silicon Valley Bank
Foundation.

                                      -7-
<PAGE>

      8. Rights as Stockholders; Information. No holder of this Amended and
Restated Warrant, as such, shall be entitled to vote or receive dividends or be
deemed the holder of Series Preferred or any other securities of the Company
which may at any time be issuable upon the exercise hereof for any purpose, nor
shall anything contained herein be construed to confer upon the holder of this
Amended and Restated Warrant, as such, any of the rights of a stockholder of the
Company or any right to vote for the election of directors or upon any matter
submitted to stockholders at any meeting thereof, or to receive notice of
meetings, or to receive dividends or subscription rights or otherwise until this
Amended and Restated Warrant shall have been exercised and the Shares
purchasable upon the exercise hereof shall have become deliverable, as provided
herein. Notwithstanding the foregoing, the Company will transmit to the holder
of this Amended and Restated Warrant such information, documents and reports as
are generally distributed to the holders of any class or series of the
securities of the Company concurrently with the distribution thereof to the
stockholders.

      9. Market Stand-Off Agreement. In connection with the IPO and upon request
of the Company or the underwriters managing such offering of the Company's
securities, the holder of this Amended and Restated Warrant agrees not sell,
dispose of, transfer, make any short sale of, grant any option for the purchase
of, or enter into any hedging or similar transaction with the same economic
effect as a sale, any Common Stock (or other securities) of the Company held by
such holder, for a period of time specified by the managing underwriter(s) (not
to exceed one hundred eighty (180) days) following the effective date of a
registration statement relating to the IPO; provided that all other persons
selling shares of Common Stock in such offering and all executive officers,
directors and one percent (1%) shareholders of the Company shall also have
agreed not to sell publicly their Common Stock under the circumstances and
pursuant to the terms set forth in this Section 9. Holder agrees to execute and
deliver such other agreements as may be reasonably requested by the Company
and/or the managing underwriter(s) which are consistent with the foregoing or
which are necessary to give further effect thereto. In order to enforce the
foregoing covenant, the Company may impose stop-transfer instructions with
respect to such Common Stock (or other securities) until the end of such period.

      10. Additional Rights.

            10.1 Acquisition Transactions. The Company shall provide the holder
of this Amended and Restated Warrant with at least twenty (20) days' written
notice prior to closing thereof of the terms and conditions of any of the
following transactions (to the extent the Company has notice thereof): (i) the
sale, lease, exchange, conveyance or other disposition of all or substantially
all of the Company's property or business, or (ii) its merger into or
consolidation with any other corporation (other than a wholly-owned subsidiary
of the Company), or any transaction (including a merger or other reorganization)
or series of related transactions, in which more than fifty percent (50%) of the
voting power of the Company is disposed of; provided that following the IPO, the
Company's obligations under this Section 10.1 shall be deemed replaced with a
requirement to give the holder of this Amended and Restated Warrant such
advanced notice as the Company is required by law to give to its stockholders
prior to any transaction of the nature described in the preceding clauses (i) or
(ii) of this Section 10.1.

                                      -8-
<PAGE>

            10.2 Right to Convert Warrant into Stock: Net Issuance.

                  (a) Right to Convert. In addition to and without limiting the
rights of the holder under the terms of this Amended and Restated Warrant, the
holder shall have the right to convert this Amended and Restated Warrant or any
portion thereof (the "Conversion Right") into shares of Series Preferred as
provided in this Section 10.2 at any time or from time to time during the term
of this Amended and Restated Warrant. Upon exercise of the Conversion Right with
respect to a specified number of shares subject to this Amended and Restated
Warrant (the "Converted Warrant Shares"), the Company shall deliver to the
holder (without payment by the holder of any exercise price or any cash or other
consideration) that number of shares of fully paid and nonassessable Series
Preferred as is determined according to the following formula:

     X = B - A
         -----
           Y

     Where: X =        the number of shares of Series Preferred that shall be
                       issued to holder

            Y =        the fair market value of one share of Series Preferred

            A =        the aggregate Warrant Price of the specified number of
                       Converted Warrant Shares immediately prior to the
                       exercise of the Conversion Right (i.e., the number of
                       Converted Warrant Shares multiplied by the Warrant Price)

            B =        the aggregate fair market value of the specified
                       number of Converted Warrant Shares (i.e., the number of
                       Converted Warrant Shares multiplied by the fair market
                       value of one Converted Warrant Share)

      No fractional shares shall be issuable upon exercise of the Conversion
Right, and, if the number of shares to be issued determined in accordance with
the foregoing formula is other than a whole number, the Company shall pay to the
holder an amount in cash equal to the fair market value of the resulting
fractional share on the Conversion Date (as hereinafter defined). For purposes
of Section 10 of this Amended and Restated Warrant, shares issued pursuant to
the Conversion Right shall be treated as if they were issued upon the exercise
of this Amended and Restated Warrant.

            (b) Method of Exercise. The Conversion Right may be exercised by the
holder by the surrender of this Amended and Restated Warrant at the principal
office of the Company together with a written statement (which may be in the
form of Exhibit A-1 or Exhibit A-2 hereto) specifying that the holder thereby
intends to exercise the Conversion Right and indicating the number of shares
subject to this Amended and Restated Warrant which are being surrendered
(referred to in Section 10.2(a) hereof as the Converted Warrant Shares) in
exercise of the Conversion Right. Such conversion shall be effective upon
receipt by the Company of this Amended and Restated Warrant together with the
aforesaid written statement, or on such later date as is specified therein (the
"Conversion Date"), and, at the election of the holder hereof, may be made
contingent upon the closing of the sale of the Company's Common Stock to the
public in a public offering pursuant to a Registration Statement under the Act
(a "Public

                                      -9-
<PAGE>

Offering"). Certificates for the shares issuable upon exercise of the
Conversion Right and, if applicable, a new warrant evidencing the balance of the
shares remaining subject to this Amended and Restated Warrant, shall be issued
as of the Conversion Date and shall be delivered to the holder within thirty
(30) days following the Conversion Date.

            (c) Determination of Fair Market Value. For purposes of this Section
10.2, "fair market value" of a share of Series Preferred (or Common Stock if the
Series Preferred has been automatically converted into Common Stock) as of a
particular date (the "Determination Date") shall mean:

                  (i) If the Conversion Right is exercised in connection with
and contingent upon a Public Offering, and if the Company's Registration
Statement relating to such Public Offering ("Registration Statement") has been
declared effective by the Securities and Exchange Commission, then the initial
"Price to Public" specified in the final prospectus with respect to such
offering.

                  (ii) If the Conversion Right is not exercised in connection
with and contingent upon a Public Offering, then as follows:

            (A) If traded on a securities exchange, the fair market value of the
Common Stock shall be deemed to be the average of the closing prices of the
Common Stock on such exchange over the five trading days immediately prior to
the Determination Date, and the fair market value of the Series Preferred shall
be deemed to be such fair market value of the Common Stock multiplied by the
number of shares of Common Stock into which each share of Series Preferred is
then convertible;

            (B) If traded on the Nasdaq Stock Market or other over-the-counter
system, the fair market value of the Common Stock shall be deemed to be the
average of the closing prices of the Common Stock as reported in the Wall Street
Journal over the five trading days immediately prior to the Determination Date,
and the fair market value of the Series Preferred shall be deemed to be such
fair market value of the Common Stock multiplied by the number of shares of
Common Stock into which each share of Series Preferred is then convertible; and

            (C) If there is no public market for the Common Stock, then fair
market value of the Common Stock shall be determined in good faith by the Board
of Directors of the Company. If there is no public market for the Series
Preferred, then fair market value of the Series Preferred shall be determined in
good faith by the Board of Directors of the Company.

In making a determination under clauses (A) or (B) above, if on the
Determination Date, five trading days had not passed since the IPO, then the
fair market value of the Common Stock shall be the average closing prices for
the shorter period beginning on and including the date of the IPO and ending on
the trading day prior to the Determination Date (or if such period includes only
one trading day the closing price for such trading day). If closing prices are
no longer reported by a securities exchange or other trading system, the closing
price shall be that which is reported by such securities exchange or other
trading system at 4:00 p.m. New York City time on the applicable trading day.

                                      -10-
<PAGE>

      10.3 Exercise Prior to Expiration. To the extent this Amended and Restated
Warrant is not previously exercised as to all of the Shares subject hereto, and
if the fair market value of one share of the Series Preferred is greater than
the Warrant Price then in effect, this Amended and Restated Warrant shall be
deemed automatically exercised pursuant to Section 10.2 (even if not
surrendered) immediately before its expiration. For purposes of such automatic
exercise, the fair market value of one share of the Series Preferred upon such
expiration shall be determined pursuant to Section 10.2(c). To the extent this
Amended and Restated Warrant or any portion thereof is deemed automatically
exercised pursuant to this Section 10.3, the Company agrees to promptly notify
the holder hereof of the number of Shares, if any, the holder hereof is to
receive by reason of such automatic exercise. The holder hereof will promptly
surrender this Amended and Restated Warrant following receipt from the Company
of certificates representing such Shares.

      11. Representations, Warranties and Covenants. The Company represents,
warrants and covenants to the holder of this Amended and Restated Warrant as
follows:

            (a) This Amended and Restated Warrant has been duly authorized and
executed by the Company and is a valid and binding obligation of the Company
enforceable in accordance with its terms, subject to laws of general application
relating to bankruptcy, insolvency and the relief of debtors and the rules of
law or principles at equity governing specific performance, injunctive relief
and other equitable remedies.

            (b) The shares of Series C-1 Preferred stock issuable upon exercise
of this Amended and Restated Warrant have been duly authorized and reserved for
issuance by the Company and, if issued in accordance with the terms hereof, will
be validly issued, fully paid and nonassessable and free from preemptive rights.

            (c) The rights, preferences, privileges and restrictions granted to
or imposed upon the Series Preferred Stock and the holders thereof are as set
forth in the Charter. Assuming this Amended and Restated Warrant is exercisable
for shares of Series C-1 Preferred Stock, on the Amended and Restated Warrant
Date, each share of the Series Preferred represented by this Amended and
Restated Warrant is convertible into one share of Common Stock. If shares of
Series Preferred are sold by the Company in a Qualified Financing following the
Amended and Restated Warrant Date and prior to the expiration or exercise of
this Amended and Restated Warrant for a purchase price of less than $8.45 per
share, the Company will authorize and reserve for issuance by the Company all
shares of Series Preferred issuable upon exercise of this Amended and Restated
Warrant and, if issued in accordance with the terms hereof, such shares of
Series Preferred will be validly issued, fully paid and nonassessable and free
from preemptive rights

            (d) The shares of Common Stock issuable upon conversion of the
Shares have been duly authorized and reserved for issuance by the Company and,
when issued in accordance with the terms of the Charter will be validly issued,
fully paid and nonassessable.

            (e) The execution and delivery of this Amended and Restated Warrant
are not, and the issuance of the Shares upon exercise of this Amended and
Restated Warrant in accordance with the terms hereof will not be, inconsistent
with the Company's Charter or by-laws, do not and will not contravene any law,
governmental rule or regulation, judgment or order applicable to the Company (in
each case as such laws, governmental rules and regulations, judgments or orders
are currently in effect), and do not and will not conflict with or contravene
any provision of, or constitute a default under, any indenture, mortgage,
contract or other

                                      -11-
<PAGE>

instrument of which the Company is a party or by which it is bound or, as of
the Amended and Restated Warrant Date, require the consent or approval of, the
giving of notice to, the registration or filing with or the taking of any action
in respect of or by, any Federal, state or local government authority or agency
or other person, except for the filing of notices pursuant to federal and state
securities laws, which filings will be effected by the time required thereby.
The Company covenants to take all necessary steps to ensure that from and after
the Amended and Restated Warrant Date the issuance of the Shares upon exercise
of this Amended and Restated Warrant in accordance with the terms hereof will
not contravene any law, governmental rule or regulation, judgment or order
applicable to the Company at any time.

            (f) As of the Original Warrant Grant Date, there were no actions,
suits, audits, investigations or proceedings pending or, to the knowledge of the
Company, threatened against the Company in any court or before any governmental
commission, board or authority which, if adversely determined, could have a
material adverse effect on the ability of the Company to perform its obligations
under this Amended and Restated Warrant.

            (g) The number of shares of Common Stock of the Company outstanding
on the Original Warrant Grant Date, on a fully diluted basis (assuming the
conversion of all outstanding convertible securities and the exercise of all
outstanding options and warrants other than this Amended and Restated Warrant
and the Other Warrants, and excluding any shares of Common Stock issuable
pursuant to that certain Convertible Promissory Note dated as of December 21,
2001, issued to Holdings Trust), did not exceed 26,184,348 shares.

      12. Modification and Waiver. This Amended and Restated Warrant and any
provision hereof may be changed, waived, discharged or terminated only by an
instrument in writing signed by the party against which enforcement of the same
is sought.

      13. Notices. Any notice, request, communication or other document required
or permitted to be given or delivered to the holder hereof or the Company shall
be delivered, or shall be sent by certified or registered mail, or by
internationally recognized overnight courier, postage prepaid, to each such
holder at its address as shown on the books of the Company or to the Company at
the address indicated therefor on the signature page of this Amended and
Restated Warrant or such other address as the Company may specify pursuant to
this Section 13. A copy of any notices sent to the Company shall be
simultaneously sent to the Company's counsel, Annette North, at the Company's
address indicated therefor on the signature page of this Amended and Restated
Warrant or such other address as the Company may specify pursuant to this
Section 13.

      14. Binding Effect on Successors. This Amended and Restated Warrant shall
be binding upon any corporation succeeding the Company by merger, consolidation
or acquisition of all or substantially all of the Company's assets, and all of
the obligations of the Company relating to the Series Preferred issuable upon
the exercise or conversion of this Amended and Restated Warrant shall survive
the exercise, conversion and termination of this Amended and Restated Warrant
and all of the covenants and agreements of the Company shall inure to the
benefit of the successors and assigns of the holder hereof.

      15. Lost Warrants or Stock Certificates. The Company covenants to the
holder hereof that, upon receipt of evidence reasonably satisfactory to the
Company of the loss, theft, destruction or mutilation of this Amended and
Restated Warrant or any stock certificate and, in

                                      -12-
<PAGE>

the case of any such loss, theft or destruction, upon receipt of an indemnity
reasonably satisfactory to the Company, or in the case of any such mutilation
upon surrender and cancellation of such Warrant or stock certificate, the
Company will make and deliver a new Amended and Restated Warrant or stock
certificate, of like tenor, in lieu of the lost, stolen, destroyed or mutilated
Warrant or stock certificate.

      16. Descriptive Headings. The descriptive headings of the various Sections
of this Amended and Restated Warrant are inserted for convenience only and do
not constitute a part of this Amended and Restated Warrant. The language in this
Amended and Restated Warrant shall be construed as to its fair meaning without
regard to which party drafted this Amended and Restated Warrant.

      17. Governing Law. This Amended and Restated Warrant shall be construed
and enforced in accordance with, and the rights of the parties shall be governed
by, the laws of the State of California, without regard to principles of
conflicts of law.

      18. Survival of Representations, Warranties and Agreements. All
representations and warranties of the Company and the holder hereof contained
herein shall survive the Original Warrant Grant Date, the exercise or conversion
of this Amended and Restated Warrant (or any part hereof) or the termination or
expiration of rights hereunder. All agreements of the Company and the holder
hereof contained herein shall survive indefinitely until, by their respective
terms, they are no longer operative.

      19. Remedies. In case any one or more of the covenants and agreements
contained in this Amended and Restated Warrant shall have been breached, the
holders hereof (in the case of a breach by the Company), or the Company (in the
case of a breach by a holder), may proceed to protect and enforce their or its
rights either by suit in equity and/or by action at law, including, but not
limited to, an action for damages as a result of any such breach and/or an
action for specific performance of any such covenant or agreement contained in
this Amended and Restated Warrant.

      20. No Impairment of Rights. The Company will not, by amendment of its
Charter or through any other means, avoid or seek to avoid the observance or
performance of any of the terms of this Amended and Restated Warrant, but will
at all times in good faith assist in the carrying out of all such terms and in
the taking of all such action as may be necessary or appropriate in order to
protect the rights of the holder of this Amended and Restated Warrant against
impairment.

      21. Severability. The invalidity or unenforceability of any provision of
this Amended and Restated Warrant in any jurisdiction shall not affect the
validity or enforceability of such provision in any other jurisdiction, or
affect any other provision of this Amended and Restated Warrant, which shall
remain in full force and effect.

      22. Recovery of Litigation Costs. If any legal action or other proceeding
is brought for the enforcement of this Amended and Restated Warrant, or because
of an alleged dispute, breach, default, or misrepresentation in connection with
any of the provisions of this Amended and Restated Warrant, the successful or
prevailing party or parties shall be entitled to recover reasonable attorneys'
fees and other costs incurred in that action or proceeding, in addition to any
other relief to which it or they may be entitled.

                                      -13-
<PAGE>

      23. Entire Agreement; Modification. This Amended and Restated Warrant
constitutes the entire agreement between the parties pertaining to the subject
matter contained in it and supersedes all prior and contemporaneous agreements,
representations, and undertakings of the parties, whether oral or written, with
respect to such subject matter.

      24. Acceptance. Acceptance of this Amended and Restated Warrant by the
holder shall constitute acceptance of and agreement to all of the terms and
conditions contained herein

      25. Amendment and Restatement of Prior Warrant. This Amended and Restated
Warrant to Purchase Series C-1 Preferred Stock supersedes and restates in its
entirety the Warrant to Purchase Shares of Preferred Stock dated July 15, 2002
(the "Prior Warrant"). Upon execution of this Amended and Restated Warrant, all
provisions of, rights granted and covenants made in the Prior Warrant are hereby
waived, released and terminated in their entirety and shall have no further
force and effect.

                            [signature page follows]

                                      -14-
<PAGE>

      The Company has caused this Amended and Restated Warrant to be duly
executed and delivered as of the Amended and Restated Warrant Date specified
above.

                                      STRUCTURAL GENOMIX, INC.

                                      By:__________________________________

                                      Name:________________________________

                                      Title:_______________________________

                                      Address: 10505 Roselle Street
                                               San Diego, California 92121

                                      -15-
<PAGE>

                                  EXHIBIT A-1

                               NOTICE OF EXERCISE

To:   STRUCTURAL GENOMIX, INC. (the "Company")

      1. The undersigned hereby:

         [ ]   elects to purchase________ shares of [Series Preferred Stock]
               [Common Stock] of the Company pursuant to the terms of the
               attached Amended and Restated Warrant, and tenders herewith
               payment of the purchase price of such shares in full, or

         [ ]   elects to exercise its net issuance rights pursuant to Section
               10.2 of the attached Amended and Restated Warrant with respect
               to________ shares of [Series Preferred Stock] [Common Stock].

      2. Please issue a certificate or certificates representing ________ shares
in the name of the undersigned or in such other name or names as are specified
below:

                                _________________________________
                                            (Name)

                                _________________________________

                                _________________________________
                                          (Address)

      3. The undersigned represents that the aforesaid shares are being acquired
for the account of the undersigned for investment and not with a view to, or for
resale in connection with, the distribution thereof and that the undersigned has
no present intention of distributing or reselling such shares, all except as in
compliance with applicable securities laws.

                                             _________________________________
                                             (Signature)

_________________________
         (Date)

<PAGE>

                                   EXHIBIT A-2

                               NOTICE OF EXERCISE

To:   STRUCTURAL GENOMIX, INC.  (the "Company")

      1. Contingent upon and effective immediately prior to the closing (the
"Closing") of the Company's public offering contemplated by the Registration
Statement on Form S___, filed________, 200_, the undersigned hereby:

      [ ] elects to purchase________shares of [Series Preferred Stock] [Common
Stock] of the Company (or such lesser number of shares as may be sold on behalf
of the undersigned at the Closing) pursuant to the terms of the attached Amended
and Restated Warrant, or

      [ ] elects to exercise its net issuance rights pursuant to Section 10.2 of
the attached Amended and Restated Warrant with respect to________ shares of
[Series Preferred Stock] [Common Stock].

      2. Please deliver to the custodian for the selling shareholders a stock
certificate representing such________shares.

      3. The undersigned has instructed the custodian for the selling
shareholders to deliver to the Company $________or, if less, the net proceeds
due the undersigned from the sale of shares in the aforesaid public offering. If
such net proceeds are less than the purchase price for such shares, the
undersigned agrees to deliver the difference to the Company prior to the
Closing.

                                           ___________________________________
                                           (Signature)

__________________
(Date)

<PAGE>

                                    EXHIBIT B

                                     CHARTER