During this fiscal year we devoted considerable efforts towards efficient highly parallel implementations of classical molecular dynamics. The highly efficient PMEMD molecular dynamics code developed and maintained by our group (in particular Robert Duke) was further developed to achieve parallel scaling out to hundreds of processors, allowing us to thoroughly simulate the large protein complexes involved in blood coagulation and related processes. We also explored and modified two recent accelerated sampling methodologies, allowing thorough exploration of conformational free energy surfaces. Importantly, these new methods open new possibilities beyond the reach of conventional molecular simulations.

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Zheng, Xunhai; Mueller, Geoffrey A; Kim, Kyungmin et al. (2017) Identification of drivers for the metamorphic transition of HIV-1 reverse transcriptase. Biochem J 474:3321-3338
Liu, Shubin; Hu, Hao; Pedersen, Lee G (2010) Steric, quantum, and electrostatic effects on S(N)2 reaction barriers in gas phase. J Phys Chem A 114:5913-8
Lee, Chang Jun; Wu, Sangwook; Eun, Changsun et al. (2010) A revisit to the one form kinetic model of prothrombinase. Biophys Chem 149:28-33
Elking, Dennis M; Perera, Lalith; Duke, Robert et al. (2010) Atomic forces for geometry-dependent point multipole and gaussian multipole models. J Comput Chem 31:2702-13
de Courcy, B; Pedersen, L G; Parisel, O et al. (2010) Understanding selectivity of hard and soft metal cations within biological systems using the subvalence concept. I. Application to blood coagulation: direct cation-protein electronic effects vs. indirect interactions through water networks. J Chem Theory Comput 6:1048-1063
Elking, Dennis M; Cisneros, G Andres; Piquemal, Jean-Philip et al. (2010) Gaussian Multipole Model (GMM). J Chem Theory Comput 6:190-202
Zurita, Adolfo; Zhang, Yinghao; Pedersen, Lee et al. (2010) Obligatory role in GTP hydrolysis for the amide carbonyl oxygen of the Mg(2+)-coordinating Thr of regulatory GTPases. Proc Natl Acad Sci U S A 107:9596-601
Lee, Chang Jun; Chandrasekaran, Vasu; Wu, Sangwook et al. (2010) Recent estimates of the structure of the factor VIIa (FVIIa)/tissue factor (TF) and factor Xa (FXa) ternary complex. Thromb Res 125 Suppl 1:S7-S10
Cisneros, G Andrés; Perera, Lalith; Schaaper, Roel M et al. (2009) Reaction mechanism of the epsilon subunit of E. coli DNA polymerase III: insights into active site metal coordination and catalytically significant residues. J Am Chem Soc 131:1550-6
Mutoh, Shingo; Osabe, Makoto; Inoue, Kaoru et al. (2009) Dephosphorylation of threonine 38 is required for nuclear translocation and activation of human xenobiotic receptor CAR (NR1I3). J Biol Chem 284:34785-92

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