A Simple and Efficient Protein Structure Refinement Method

Improving the quality of a given protein structure can serve as the ultimate solution for accurate protein structure prediction, and seeking such a method is currently a challenge in computational structural biology. In order to promote and encourage much needed such efforts, CASP (Critical Assessment of Structure Prediction) has been providing an ideal computational experimental platform, where it was reported only recently (since CASP10) that systematic protein structure refinement is possible by carrying out extensive (approximately millisecond) MD simulations with proper restraints generated from the given structure. Using an explicit solvent model and much reduced positional and distance restraints than previously exercised, we propose a refinement protocol that combines a series of short (5 ns) MD simulations with energy minimization procedures. Testing and benchmarking on 54 CASP8-10 refinement targets and 34 CASP11 refinement targets shows quite promising results. Using only a small fraction of MD simulation steps (nanosecond versus millisecond), systematic protein structure refinement was demonstrated in this work, indicating that refinement of a given model can be achieved using a few hours of desktop computing.