Systematic Assessment of the Effects of an All-Atom Force Field and the Implicit Solvent Model on the Refinement of NMR Structures with Subsets of Distance Restraints

Abstract

Jun-Goo JeeResearch Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, Daegu 702-701, Korea. E-mail: jjee@knu.ac.krReceived February 22, 2014, Accepted March 5, 2014Employment of a time consuming, sophisticated calculation using the all-atom force field and generalized-Born implicit solvent model (GBIS) for refinement of NMR structures has become practical through advancesin computational methods and capacities. GBIS refinement improves the qualities of the resulting NMRstructures with reduced computational times. However, the contribution of GBIS to NMR structures has notbeen sufficiently studied in a quantitative way. In this paper, we report the effects of GBIS on the refined NMRstructures of ubiquitin (UBQ) and GB1 with subsets of distance restraints derived from experimental data.Random omission prepared a series of distance restraints 0.05, 0.1, 0.3, 0.5, and 0.7 times smaller. For eachnumber, we produced five different restraints for statistical analysis. We then recalculated the NMR structuresusing CYANA software, followed by GBIS refinements using the AMBER package. GBIS improved both theprecision and accuracy of all the structures, but to varied levels. The degrees of improvement were significantwhen the input restraints were insufficient. In particular, GBIS enabled GB1 to form an accurate structure evenwith distance restraints of 5%, revealing that the root-mean-square deviation was less than 1 A from the X-raybackbone structure. We also showed that the efficiency of searching the conformational space was moreimportant for finding accurate structures with the calculation of UBQ with 5% distance restraints than thenumber of conformations generated. Our data will provide a meaningful guideline to judge and compare thestructural improvements by GBIS. Key Words : NMR, Generalized-Born implicit solvent model, Ubiquitin, GB1IntroductionSteady advances in algorithms for both NOE assignmentsand structure calculations have made automatic calculationsof protein 3D structures with raw NOE data, provided thechemical shifts are assigned for most atoms and sufficientpeaks exist.