Additional file 2 of Synergy between trastuzumab and pertuzumab for human epidermal growth factor 2 (Her2) from colocalization: an in silicobased mechanism
Creators: name: Fuentes, Gloria
name: Scaltriti, Maurizio
name: Baselga, José
name: Verma, Chandra S
Publisher: name: figshare
Year: 2020
Subjects: subject: Biochemistry
subject: Medicine
subject: Molecular Biology
subject: Pharmacology
subject: Evolutionary Biology
subject: FOS: Biological sciences
subject: FOS: Biological sciences
subject: Immunology
subject: FOS: Clinical medicine
subject: FOS: Clinical medicine
subject: 69999 Biological Sciences not elsewhere classified
subject: 19999 Mathematical Sciences not elsewhere classified
subject: FOS: Mathematics
subject: FOS: Mathematics
subject: Cancer
subject: Hematology
subject: 110309 Infectious Diseases
subject: FOS: Health sciences
subject: FOS: Health sciences
subject: 60506 Virology
subject: Computational Biology

description: Additional file 2: Supplemental Figure S2. The characterization of the collective protein dynamics have been analyzed using Principal Component Analysis (PCA). PCA is a statistical method that highlight similarities and differences in a complex data set by reducing the number of dimensions without losing much of the information. In MD simulations, the application of PCA can separate the configurational space into two subspaces; the essential one containing the functionally important correlated motions (comprising only few degrees of freedom or eigenvectors) and the irrelevant subspace with the independent Gaussian fluctuations with little functional relevance. In this study, PCA has been performed on an ensemble of conformations derived from the different MD simulations. Results of PCA obtained from the diagonalization of the atomic displacement correlation matrix of Cα atoms of the ectodomain from six of the MD simulations carried out in this study (using standard Euclidean distances) are shown here. The resulting Principal Components (PCs) are sorted according to their contribution to the total fluctuation along the ensemble of conformations, and only a small subset of these PCs are necessary to describe the great majority of the total atomic displacements which capture the essential dynamics of the conformational changes occurring in the system (the above so-referred essential subspace). Every figure contains the percentage of the cumulative eigenvalues as a function of the number of eigenvectors considered. The inset includes the projection on the first two eigenvectors of the coordinates extracted from the time interval of 8 to 16 ns. Every figure represents the coordinates for the ectodomain of Her2 from the following simulations: (A) apo Her2; (B) Her2:pertuzumab:trastuzumab; (C) Her2:pertuzumab; (D) Her2:trastuzumab; (E) apo truncated Her2; (F) truncated Her2:pertuzumab:trastuzumab. The application of PCA on data obtained from MD simulations provides a useful way of detecting global, correlated motions of the system that are separate from the tightly-constrained harmonic motions of more constrained atoms. The structures projected on the first eigenvectors have facilitated our understanding of the dynamics of the six systems analysed here (see Supplementary Figure S6). (PDF 746 KB)