Journal ArticleDOI
Efficient Monte Carlo method for simulation of fluctuating conformations of native proteins.
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TLDR
A powerful Monte Carlo method is described to simulate thermal conformational fluctuations in native proteins by using an empirical conformational energy function in which bond lengths and bond angles are kept fixed and only dihedral angles are independent variables.Abstract:
A powerful Monte Carlo method is described to simulate thermal conformational fluctuations in native proteins by using an empirical conformational energy function in which bond lengths and bond angles are kept fixed and only dihedral angles are independent variables. In this method, collective variables corresponding to eigenvectors of the second-derivative matrix of the energy function at its minimum point are scaled according to corresponding eigenvalues in such a way that the energy function in terms of the scaled collective variables is isotropic at the minimum point. Simulation is carried out with an isotropic step size in the space of these scaled collective variables. This simulation method is applied to a small protein, bovine pancreatic trypsin inhibitor (BPTI), and its model harmonic system defined by a quadratic energy function with the same second-derivative matrix as that of BPTI at its minimum point. Efficiency of the simulation method with an isotropic step size in the space of the scaled collective variables is found to be about 500–50 times greater than the conventional method with with an isotropic step in the space of the usual nonscaled variables. One step of this new method generates conformational changes that occur in the real-time range of 0.05 ps. In a record of 5 × 105 step simulation, the BPTI molecule is observed to migrate beyond a single minimum-energy region.read more
Citations
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Journal ArticleDOI
Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome.
Marco Tartaglia,Marco Tartaglia,Ernest L. Mehler,Rosalie Goldberg,Giuseppe Zampino,Han G. Brunner,Hannie Kremer,Ineke van der Burgt,Andrew H. Crosby,Andra Ion,Steve Jeffery,Kamini Kalidas,Michael A. Patton,Raju Kucherlapati,Bruce D. Gelb +14 more
TL;DR: It is shown that missense mutations in PTPN11—a gene encoding the nonreceptor protein tyrosine phosphatase SHP-2, which contains two Src homology 2 (SH2) domains—cause Noonan syndrome and account for more than 50% of the cases that were examined.
Journal ArticleDOI
ICM—a new method for protein modeling and design: applications to docking and structure prediction from the distorted native conformation
TL;DR: It is concluded that the most promising detailed approach to the protein‐folding problem would consist of some coarse global sampling strategy combined with the local energy minimization in the torsion coordinate space.
Journal ArticleDOI
Biased probability Monte Carlo conformational searches and electrostatic calculations for peptides and proteins.
Ruben Abagyan,Maxim Totrov +1 more
TL;DR: An efficient way to make a random step in a Monte Carlo procedure given knowledge of the energy or statistical properties of conformational subspaces is found, and the BPMC procedure is applied to the structure prediction of 12- and 16-residue synthetic peptides and the determination of protein structure from NMR data.
Journal ArticleDOI
Investigating protein dynamics in collective coordinate space.
Akio Kitao,Nobuhiro Go +1 more
TL;DR: Collective coordinates have been successfully applied to finding functionally relevant motions, to investigating the physical nature of protein dynamics, to sampling of the conformational space and to the analysis of experimental data.
Journal ArticleDOI
Representing Receptor Flexibility in Ligand Docking through Relevant Normal Modes
TL;DR: It is shown that only very few modes in the low-frequency range are necessary and sufficient to describe loop flexibility in cAMP-dependent protein kinase and introduced a measure of relevance of normal modes on a given region of interest.
References
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Some Studies Concerning Rotating Axes and Polyatomic Molecules
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Journal ArticleDOI
Harmonic dynamics of proteins: normal modes and fluctuations in bovine pancreatic trypsin inhibitor.
Bernard R. Brooks,Martin Karplus +1 more
TL;DR: The analysis demonstrates that, in spite of the anharmonic contributions to the potential, a normal mode description can provide useful results concerning the internal motions of proteins.
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