bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exact rotamer optimization for protein design
Authors: Gordon D. Benjamin , Hom Geoffrey K. , Mayo Stephen L. , Pierce Niles A. 
Published: December 2002

AbstractComputational methods play a central role in the rational design of novel proteins. The present work describes a new hybrid exact rotamer optimization (HERO) method that builds on previous dead‐end elimination algorithms to yield dramatic performance enhancements. Measured on experimentally validated physical models, these improvements make it possible to perform previously intractable designs of entire protein core, surface, or boundary regions. Computational demonstrations include a full core design of the variable domains of the light and heavy chains of catalytic antibody 48G7 FAB with 74 residues and 10128 conformations, a full core/boundary design of the β1 domain of protein G with 25 residues and 1053 conformations, and a full surface design of the β1 domain of protein G with 27 residues and 1060 conformations. In addition, a full sequence design of the β1 domain of protein G is used to demonstrate the strong dependence of algorithm performance on the exact form of the potential function and the fidelity of the rotamer library. These results emphasize that search algorithm performance for protein design can only be meaningfully evaluated on physical models that have been subjected to experimental scrutiny. The new algorithm greatly facilitates ongoing efforts to engineer increasingly complex protein features. © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 232–243, 2003
An improved method for nonbonded list generation: Rapid determination of near‐neighbor pairs
Authors: Petrella Robert J. , Andricioaei Ioan , Brooks Bernard R. , Karplus Martin 
Published: December 2002

AbstractGeneration of the list of near‐neighbor pairs of atoms not bonded to each other is a key feature of many programs for calculating the energy and energy derivatives for large molecules. Because this step can take a significant amount of CPU time, more efficient nonbonded list generation can speed up the energy calculations. In this article, a novel nonbonded list generation algorithm, BYCC, is introduced. It combines certain features of other algorithms and achieves more rapid nonbonded list generation; a factor of ≈2.5 for a molecule of 5000 atoms with a cutoff in the 10 Å range is obtained on Hewlett‐Packard (HP) and Alpha processors, without greatly increasing memory requirements. © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 222–231, 2003
Development of a polarizable force field for proteins via ab initio quantum chemistry: First generation model and gas phase tests
Authors: Kaminski George A. , Stern Harry A. , Berne B. J. , Friesner Richard A. , Cao Yixiang X. , Murphy Robert B. , Zhou Ruhong , Halgren Thomas A. 
Published: December 2002

AbstractWe present results of developing a methodology suitable for producing molecular mechanics force fields with explicit treatment of electrostatic polarization for proteins and other molecular system of biological interest. The technique allows simulation of realistic‐size systems. Employing high‐level ab initio data as a target for fitting allows us to avoid the problem of the lack of detailed experimental data. Using the fast and reliable quantum mechanical methods supplies robust fitting data for the resulting parameter sets. As a result, gas‐phase many‐body effects for dipeptides are captured within the average RMSD of 0.22 kcal/mol from their ab initio values, and conformational energies for the di‐ and tetrapeptides are reproduced within the average RMSD of 0.43 kcal/mol from their quantum mechanical counterparts. The latter is achieved in part because of application of a novel torsional fitting technique recently developed in our group, which has already been used to greatly improve accuracy of the peptide conformational equilibrium prediction with the OPLS‐AA force field.1 Finally, we have employed the newly developed first‐generation model in computing gas‐phase conformations of real proteins, as well as in molecular dynamics studies of the systems. The results show that, although the overall accuracy is no better than what can be achieved with a fixed‐charges model, the methodology produces robust results, permits reasonably low computational cost, and avoids other computational problems typical for polarizable force fields. It can be considered as a solid basis for building a more accurate and complete second‐generation model. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 1515–1531, 2002
Consistent treatment of inter‐ and intramolecular polarization in molecular mechanics calculations
Authors: Ren Pengyu , Ponder Jay W. 
Published: December 2002

AbstractA protocol is described for the treatment of molecular polarization in force field calculations. The resulting model is consistent in that both inter‐ and intramolecular polarization are handled within a single scheme. An analytical formula for removing intramolecular polarization from a set of atomic multipoles for an arbitrary static structure or conformation is given. With the help of the intramolecular polarization, these permanent atomic multipoles can then be applied in modeling alternative conformations of a molecule. Equipped with this simple technique, one can derive transferable electrostatic parameters for peptides and proteins using flexible model compounds such as dipeptides. The proposed procedure is tested for its ability to describe the electrostatic potential around various configurations of theN‐methylacetamide dimer. The effect of different intramolecular polarization schemes on the accuracy of a force field model of the electrostatic potential of alanine dipeptide is investigated. A group‐based scheme for including direct intramolecular polarization is shown to be most successful in accounting for the conformational dependence of electrostatic potentials. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 1497–1506, 2002
Parallel stored‐integral and semidirect Hartree–Fock and DFT methods with data compression
Authors: Mitin Alexander V. , Baker Jon , Wolinski Krzysztof , Pulay Peter 
Published: December 2002

AbstractRecent developments in magnetic disk technology have made stored‐integral techniques competitive with the currently more widely used direct methods, which involve the recalculation of the basic two‐electron integrals. We present efficient conventional (all integrals stored) and semidirect Hartree–Fock and DFT algorithms with data compression for single‐processor and distributed memory parallel computers, and compare them with the corresponding direct algorithms. On inexpensive modern personal computer‐based hardware, the stored integral method is up to three times more efficient than the direct method in terms of total elapsed job time. © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 154–160, 2003
Molecular dynamics simulations of the dinuclear zinc‐β‐lactamase from Bacteroides fragilis complexed with imipenem
Authors: Suárez Dimas , Díaz Natalia , Merz Kenneth M. 
Published: December 2002

AbstractHerein, we present results from MD simulations of the Michaelis complex formed between the dizinc β‐lactamase from B. fragilis and imipenem. We considered two catalytically important configurations, which differ in the presence or absence of a hydroxide bridge connecting the two zinc ions in the active site. The structural and dynamical effects induced by substrate binding, the specific roles of the conserved residues and the zinc‐bound water molecules, the near attack conformers of the Michaelis complex, and so forth, are discussed in detail. The relative stability of the two configurations was estimated from QM linear scaling calculations on the enzyme‐substrate complex combined with Poisson‐Boltzmann electrostatic calculations and normal mode calculations. Importantly, we find that the two configurations have similar energies, indicating that these two structures could readily be interchanged, thereby facilitating catalysis. The configuration with the hydroxide bound to the two zinc ions is predicted to be the resting form of the enzyme, while the configuration without the bridge is the reactive form that was found to place the hydroxide in position to attack the carbonyl of the β‐lactam ring. Thus, we propose that the enzyme initiates catalysis by converting from the hydroxide bridge form into the configuration that lacks the hydroxide bridge. This interconversion increases the nucleophilicity of the hydroxide ion and exposes it to the β‐lactam carbonyl, which ultimately facilitates nucleophilic attack. The implications of the observed modes of binding, the possible influence of mutating the Lys184 and Asn193 residues on substrate binding, and the reaction mechanism are also discussed in detail. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 1587–1600, 2002
An ab initio force field for the cofactors of bacterial photosynthesis
Authors: Ceccarelli Matteo , Procacci Piero , Marchi Massimo 
Published: December 2002

AbstractThis article presents a new ab initio force field for the cofactors of bacterial photosynthesis, namely quinones and bacteriochlorophylls. The parameters has been designed to be suitable for molecular dynamics simulations of photosynthetic proteins by being compatible with the AMBER force field. To our knowledge, this is the first force field for photosynthetic cofactors based on a reliable set of ab initio density functional reference data for methyl bacteriochlorophyll a, methyl bacteriopheophytin a, and of a derivative of ubiquinone. Indeed, the new molecular mechanics force field is able to reproduce very well not only the experimental and ab initio structural properties and the vibrational spectra of the molecules, but also the eigenvectors of the molecular normal modes. For this reason it might also be helpful to understand vibrational spectroscopy results obtained on reaction center proteins. © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 129–142, 2003
Endothelial cell–Matrix interactions
Authors: Iivanainen Erika , Kähäri Veli‐Matti , Heino Jyrki , Elenius Klaus 
Published: December 2002

AbstractDynamic interactions between endothelial cells and components of their surrounding extracellular matrix are necessary for the invasion, migration, and survival of endothelial cells during angiogenesis. These interactions are mediated by matrix receptors that initiate intracellular signaling cascades in response to binding to specific extracellular matrix molecules. The interactions between endothelial cells and their environment are also modulated by enzymes that degrade different matrix components and thus enable endothelial invasion. Recent reports on gene targeting in mice have confirmed the role of two classes of matrix receptors, integrins and cell surface heparan sulfate proteoglycans, and a group of matrix degrading proteolytic enzymes, matrix metalloproteinases, in angiogenesis. The significance of endothelial cell–matrix interactions is further supported by several ongoing clinical trials that analyze the effects of drugs blocking this interaction on angiogenesis‐dependent growth of human tumors. Microsc. Res. Tech. 60:13–22, 2003. © 2002 Wiley‐Liss, Inc.
Genetic abnormalities of the endothelium
Authors: Butany Jagdish W. , Verma Subodh , Leask Richard L. , Mohsen Basal , Asa Sylvia L. 
Published: December 2002

AbstractEndothelial cell dysfunction plays an important role in the development and progression of cardiovascular and other disease. The purpose of this review is to discuss some of the genetic diseases known to adversely affect endothelial function. Although the list is exhaustive, we focus our discussion on primary pulmonary hypertension, diabetes mellitus, Alzheimer's disease, Crohn's disease, Von‐Hippel‐Lindau disease, familial Mediterranean fever, thrombotic microangiopathy, and key vascular malformations. Endothelial dysfunction results from a complex interplay between genetic and environmental factors. This review highlights some of the growing body of evidence implicating endothelial dysfunction as an important mediator of diverse diseases. Microsc. Res. Tech. 60:30–37, 2003. © 2002 Wiley‐Liss, Inc.
Mast cells and angiogenesis
Authors: Hiromatsu Yuji , Toda Shuji 
Published: December 2002

AbstractThere is much evidence that angiogenesis is related to mast cells. Mast cells accumulate in many angiogenesis‐dependent situations, including tumor growth, rheumatoid arthritis, ovulation, would healing, and tissue repair. Several mast cell mediators are angiogenic and regulate endothelial cell proliferation and function. Stem cell factor, vascular endothelial growth factor, epidermal growth factor, basic fibroblast growth factor, and platelet‐derived growth factor induce chemotactic migration of mast cells to sites of neovascularization. Mast cell products such as tryptase also degrade connective tissue matrix to provide space for neovascular sprouts. Angiogenesis has been proposed as a target for anticancer therapy and for treatment of inflammatory disorders such as rheumatoid arthritis. Future studies on the cascade of angiogenic events, including mast cell–target cell interaction, and various intracellular signaling pathways are indicated to provide a new approach for the treatment of cancer and inflammatory disorders and for tissue repair. Microsc. Res. Tech. 60:64–69, 2003. © 2002 Wiley‐Liss, Inc.
Role of growth factors and their receptors in proliferation of microvascular endothelial cells
Authors: Suhardja Agustinus , Hoffman Howard 
Published: December 2002

AbstractInvestigations over the last decade have established the essential role of growth factors and their receptors during angiogenesis. The biological significance of VEGF, EGF, and bFGF is mediated by their receptors, which belong to the family of tyrosine kinase receptors: Flt‐1 (VEGFR‐1), KDR (VEGFR‐2), EGFR, FGFR‐1, FGFR‐2, FGFR‐3, and FGFR‐4. Deeper understanding of the mechanism of activation of these growth factor receptors has allowed the development of a new pharmacological strategy aimed at controlling cancer cell proliferation. The results of a large body of preclinical as well as early clinical studies conducted suggest that targeting the growth factor receptors could represent a significant contribution to cancer therapy. Microsc. Res. Tech. 60:70–75, 2003. © 2002 Wiley‐Liss, Inc.
Effects of steroid hormones on vascular functions
Authors: Suzuki Takashi , Nakamura Yasuhiro , Moriya Takuya , Sasano Hironobu 
Published: December 2002

AbstractThe purpose of this review is to present reported findings of effects of steroids on vascular function and to discuss the biological significance in vascular physiology and pathology. Steroid hormones play various roles in vascular functions through the specific receptor localized in the endothelium and underlying vascular smooth muscle cells (VSMCs). Estrogen replacement therapy in postmenopausal women is in general associated with a reduction in mortality from cardiovascular disease and the beneficial effects of estrogens are caused by modulation of lipid metabolism, expression of leukocyte adhesion molecules, and migration of VSMCs in the vascular wall. Estrogens also play a role as vasodilators through an increment in nitric oxide (NO) production in endothelium or modulation of calcium homeostasis in VSMCs. Some progestin molecules partially oppose the effects of estrogens on vascular functions, but striking differences exist among the types of molecules. Testosterone shows a vasorelaxant response, but detailed actions of androgens on vascular functions remain unknown. Glucocorticoids act on vasoconstriction through reduced prostacyclin production, increased α‐adrenoceptor numbers, and inhibition of NO synthase, while mineralocorticoids induce hypertrophy and hyperplasia of VSMCs and perivascular fibrosis and cause peripheral vascular resistance, in addition to changes in vascular electrocyte permeability. Some rapid actions of steroids are mediated by “nongenomic” responses in vascular tissues. Recent studies have also demonstrated that steroid‐producing or ‐metabolizing enzymes are expressed in the vascular wall, suggesting the local regulation of steroids in the vascular system. Thus, steroid hormones greatly influence vascular functions and an understanding of the mechanisms may provide new means to prevent vascular diseases. Microsc. Res. Tech. 60:76–84, 2003. © 2002 Wiley‐Liss, Inc.
Automated quantitative evaluation of diseased and nondiseased renal transplants with MR renography
Authors: de Priester Jacobus A. , den Boer Jacques A. , Christiaans Maarten H.L. , Kessels Alphons G.H. , Giele Eelco L.W. , Hasman Arie , van Hooff Hans P. , van Engelshoven Jos M.A. 
Published: December 2002

AbstractPurposeTo present a method of automated parametric quantification of dynamic MR enhancement curves of renal transplants and evaluate the disease‐discriminating properties of the resulting MR renography (MRR) data.Materials and MethodsThis study included 27 patients with nondiseased renal transplants and eight patients with diseased renal transplants. The examination was repeated in 10 patients and the reproducibility of the enhancement parameters was estimated by analysis of variance (ANOVA). The disease‐discriminating properties of the transplant volumes and enhancement parameters were tested with t‐tests and logistic regression analysis.ResultsThe enhancement parameters were reproducible. The mean medullary nephronal washout rate (λ1) and cortical arterial blood volume (μ0) were lower in diseased renal transplants. The combination of these parameters was a strong predictor of renal transplant disease (area under ROC curve 0.98; 95% confidence interval 0.96–1.0).ConclusionAutomated parametric quantification of cortical and medullary enhancement is feasible and allows the accurate detection of nonsurgical disease in renal transplants by MRR. J. Magn. Reson. Imaging 2003;17:95–103. © 2002 Wiley‐Liss, Inc.
MRI/MRS evaluation of cariporide in a canine long‐term model of reperfused ischemic insults
Authors: Thompson Kerry , Wisenberg Gerald , Sykes RVT Jane , Thompson R. Terry 
Published: December 2002

AbstractPurposeTo examine with magnetic resonance imaging (MRI)/magnetic resonance spectroscopy (MRS) the long‐term effects of cariporide in a canine cardiac ischemia/reperfusion model.Materials and MethodsTwenty‐two beagles underwent a 2‐hour occlusion followed by 10 days of reperfusion. Cine MRI and 31P MRS were performed to monitor function and metabolism of the heart in the control (N = 10) and cariporide (N = 12) groups. Radioactively labeled microspheres were injected to determine coronary blood flow, and contrast‐enhanced ex vivo MRI assessed infarct volumes.ResultsCariporide produced a significant reduction vs. controls, in intracellular pH, during ischemia (P < 0.05) and at days 3 and 10 postreperfusion (P < 0.0005). Functional recovery of the myocardium was significantly improved immediately upon reperfusion (percent of baseline: 63.5% ± 3.5% for controls, 90.5% ± 7.2% for cariporide) and at day 3, but not by day 10. Normalized infarct ratios (IRs) were similar for controls and cariporide (0.58 ± 0.08, 0.58 ± 0.06, respectively).ConclusionCariporide augments early functional recovery, while delaying normalization of intracellular pH following ischemia/reperfusion, but confers neither long‐term functional or metabolic protection nor, most importantly, myocardial salvage. J. Magn. Reson. Imaging 2003;17:136–141. © 2002 Wiley‐Liss, Inc.
Diffusion tensor MRI of myocardial fibers and sheets: Correspondence with visible cut‐face texture
Authors: Tseng Wen‐Yih I. , Wedeen Van J. , Reese Timothy G. , Smith R. Neal , Halpern Elkan F. 
Published: December 2002

AbstractPurposeTo test the hypothesis that the primary, secondary, and tertiary eigenvectors of the diffusion tensor (DT) measured with DT‐MRI correspond to the fiber, sheet, and sheet normal directions, respectively, we compared DT‐MRI data with the texture visible in the cut face of fresh bovine myocardium.Materials and MethodsDT‐MRI and optical images obtained under identical conditions were compared objectively. Ink prints were made of the cut tissue, and the local orientations within these images were defined by analysis of local autocorrelations for regions matching DT‐MRI pixels. Deviation angles between the cleavage orientations and the diffusion eigenvectors were analyzed in eight specimens sliced in three orthogonal planes.ResultsRoot‐mean‐square (RMS) angular disparity was 11° between the first eigenvectors of the DT and the fiber direction, 14° between the second eigenvector and the sheet direction, 14° between the third eigenvector and the sheet normal direction, and 15° between the tensor orientation in the imaging plane and the cleavage orientation of the cut face.ConclusionThe results support a parallel relationship between the eigenvectors of the DT and symmetry axes of the myocardial architecture. Specifically, the first, second and third eigenvectors correspond to the fiber, sheet, and sheet normal directions, respectively. J. Magn. Reson. Imaging 2003;17:31–42. © 2002 Wiley‐Liss, Inc.
Proton spin‐lock ratio imaging for quantitation of glycosaminoglycans in articular cartilage
Authors: Regatte Ravinder Reddy , Akella Sarma V.S. , Borthakur Arijitt , Reddy Ravinder 
Published: December 2002

AbstractPurposeTo quantify glycosaminoglycans (GAG) in intact bovine patellar cartilage using the proton spin‐lock ratio imaging method. This approach exploits spin‐lattice relaxation time in the rotating frame (T1ρ) imaging and T1ρ relaxivity (R1ρ).Materials and MethodsAll the magnetic resonance imaging (MRI) experiments were performed on a 4‐T whole‐body GE Signa scanner (GEMS, Milwaukee, WI), and spectroscopy experiments of chondroitin sulfate (CS) phantoms were done on a 2‐T custom‐built spectrometer. A custom‐built 11‐cm‐diameter transmit‐receive birdcage coil, which was tuned to a proton frequency of 170 MHz, was employed for the imaging experiments. T1ρ measurements were made using a fast spin echo (FSE) sequence pre‐encoded with a three‐pulse cluster consisting of two 90° hard pulses separated by a low‐power rectangle pulse for spin‐locking.ResultsThe methodology is first validated on CS phantoms and then used to quantify GAG content in intact bovine cartilage (N = 5). There is a good agreement between the GAG map calculated from the T1ρ ratio imaging method (71 ± 4%) and GAG measured from spectrophotometric assay (75 ± 5%) in intact bovine tissue.ConclusionWe have demonstrated a proton spin‐lock ratio imaging method to quantify absolute GAG distribution in the cartilage in a noninvasive and nondestructive manner. J. Magn. Reson. Imaging 2003;17:114–121. © 2002 Wiley‐Liss, Inc.