Prediction of Protein Loop Conformations Using the AGBNP Implicit Solvent Model and Torsion Angle Sampling

Citations Over TimeTop 10% of 2008 papers

Abstract

The OPLS-AA all-atom force field and the Analytical Generalized Born plus Non-Polar (AGBNP) implicit solvent model, in conjunction with torsion angle conformational search protocols based on the Protein Local Optimization Program (PLOP), are shown to be effective in predicting the native conformations of 57 9-residue and 35 13-residue loops of a diverse series of proteins with low sequence identity. The novel nonpolar solvation free energy estimator implemented in AGBNP augmented by correction terms aimed at reducing the occurrence of ion pairing are important to achieve the best prediction accuracy. Extended versions of the previously developed PLOP-based conformational search schemes based on calculations in the crystal environment are reported that are suitable for application to loop homology modeling without the crystal environment. Our results suggest that in general the loop backbone conformation is not strongly influenced by crystal packing. The application of the temperature Replica Exchange Molecular Dynamics (T-REMD) sampling method for a few examples where PLOP sampling is insufficient are also reported. The results reported indicate that the OPLS-AA/AGBNP effective potential is suitable for high-resolution modeling of proteins in the final stages of homology modeling and/or protein crystallographic refinement.

Related Papers

• → An Efficient Mean Solvation Force Model for Use in Molecular Dynamics Simulations of Proteins in Aqueous Solution(1996)125 cited
• → Molecular Dynamics Simulations of Proteins: Can the Explicit Water Model Be Varied?(2007)71 cited
• → Implicit Solvation Parameters Derived from Explicit Water Forces in Large-Scale Molecular Dynamics Simulations(2012)24 cited
• → Conformational Solvation Studies of LIGNOLs with Molecular Dynamics and Conductor-Like Screening Model(2012)6 cited
• → Performance of molecular dynamics simulation for predicting of solvation free energy of neutral solutes in methanol(2021)7 cited