Protein structure prediction with the UNRES force-field using Replica-Exchange Monte Carlo-with-Minimization; Comparison with MCM, CSA, and CFMC

Two current methods of global optimization are coupled to produce the Replica‐Exchange method together with Monte Carlo‐with‐Minimization (REMCM). Its performance is compared with each separate component and with other global optimization techniques. REMCM was applied to search the conformational space of coarse grain protein systems described by the UNRES force field. The method consists of several noninteracting copies of Monte Carlo simulation, and minimization was used after every perturbation to enhance the sampling of low‐energy conformations. REMCM was applied to five proteins of different topology, and the results were compared to those from other optimization methods, namely Monte Carlo‐with‐Minimization (MCM), Conformational Space Annealing (CSA), and Conformational Family Monte Carlo (CFMC). REMCM located global minima for four proteins faster and more consistently than either MCM or CFMC, and it converged faster than CSA for three of the five proteins tested. A performance comparison was also carried out between REMCM and the traditional Replica Exchange method (REM) for one protein, with REMCM showing a significant improvement. Moreover, because of its simplicity, REMCM was easy to implement, thereby offering an alternative to other global optimization methods used in protein structure prediction. © 2005 Wiley Periodicals, Inc. J Comput Chem 26: 1472–1486, 2005