A coarse‐grained protein force field for folding and structure prediction

Abstract

We have revisited the protein coarse-grained optimized potential for efficient structure prediction (OPEP). The training and validation sets consist of 13 and 16 protein targets. Because optimization depends on details of how the ensemble of decoys is sampled, trial conformations are generated by molecular dynamics, threading, greedy, and Monte Carlo simulations, or taken from publicly available databases. The OPEP parameters are varied by a genetic algorithm using a scoring function which requires that the native structure has the lowest energy, and the native-like structures have energy higher than the native structure but lower than the remote conformations. Overall, we find that OPEP correctly identifies 24 native or native-like states for 29 targets and has very similar capability to the all-atom discrete optimized protein energy model (DOPE), found recently to outperform five currently used energy models.

Structure and Thermodynamics of Amylin Dimer Studied by Hamiltonian-Temperature Replica Exchange Molecular Dynamics Simulations

“…The intra-and interpeptide interactions are described using the coarse-grained force field OPEP version 3.2. 32 In this force field, amino acids are represented by all the heavy backbone atoms, CR, N, C, and O, as well as the amine hydrogen H and a single centroid for the side chains of the amino acids except the proline which is represented by all heavy atoms. OPEP's parameters are described in detail in refs 32 and 33.…”

“…The simulations are performed by Hamiltonian-temperature replica exchange molecular dynamics (HT-REMD) which is a modified version of the temperature REMD (T-REMD) method, 31 combined with a coarse-grained protein force field (OPEP-the Optimized Potential for Efficient peptide structure Prediction). 32 …”

Replica Exchange Molecular Dynamics Simulations of Coarse-grained Proteins in Implicit Solvent

“…OPEP, one of the best protein force fields to recognize native from decoys, 20 has already been coupled to Monte-Carlo 21,22 and MD simulations 23,24 as well as the activation-relaxation technique (ART) 25,26 to study protein folding [27][28][29][30] and the aggregation of amyloid-forming peptides. [31][32][33][34] MD-OPEP was found to describe protein dynamics at least qualitatively correctly since the absence of explicit solvent accelerates folding times by about 2 orders of magnitude compared with simulations in explicit water.…”

“…For the alanine-based and BBA systems, we use db ) 0.1 and ssm ) 0.2 , with equal to the OPEP ij parameter defined in eq 6 of ref 20, and following previous studies, 41,42 k ) 6, m ) 3, and n ) 2.…”

“…Although this seven-residue peptide does not exist in nature, it is one repeat (abcdefg, containing hydrophobic residues at positions a and d and polar residues generally elsewhere) used by proteins to form R-helical coiled coil structures. 86 In addition, it shares the same amino acid length as the Alzheimer's fragment A (16)(17)(18)(19)(20)(21)(22) known to form amyloid fibrils in vitro. 87 Therefore, this peptide represents an ideal system to demonstrate that OPEP, used to study protein aggregation, is not biased toward the formation of -sheets.…”