Molecular dynamics simulation with improved polarized protein-specific charge

• Main Author: Wei, Caiyi
• Other Authors: Zhang Dawei
• Format: Theses and Dissertations
• Language: English
• Published: 2013
• Subjects: DRNTU::Science::Chemistry::Physical chemistry::Quantum chemistry; DRNTU::Science::Biological sciences::Biochemistry; DRNTU::Science::Chemistry::Physical chemistry::Molecular structure and bonding; DRNTU::Science::Chemistry::Analytical chemistry::Proteins
• Online Access: https://hdl.handle.net/10356/53521
• Institution: Nanyang Technological University

Development of force fields is important for investigating various biological processes by using molecular dynamics simulations. The majority of the force fields treat the electronic polarizability implicitly, which limit the accuracy of molecular models for some biological systems. One newly developed force field termed polarized protein specific charge (PPC) contains an accurate description of electrostatic polarization effect, which is a vast improvement in developing force fields. In this thesis, the new force field is applied in molecular dynamics simulations to investigate the role of electrostatic polarization effect in these simulation processes. Three different PPC charges calculation strategies were designed: 3-step charge update scheme, on-the-fly charge update scheme and static charges. Since protein structure dramatically changes during the folding period, static and conformational-depended charges are not able to characterize the real electronic distribution in accordance to immediate protein structure. Therefore, the first two schemes, which periodically update charges, were used in Trp-cage protein and polyalanine peptides folding simulations, respectively. The thermodynamic properity of Trp-cage protein was better predicted by considering the polarizability. The calculated melting temperature Tm≈325K was in close agreement with experimental results. In folding studies of polyalanine peptides, the native protein conformations are better predicted by considering the important electrostatic polarizability in protein folding performances. For the third charge calculation strategy: static PPC charges are feasible in studying a protein system without large conformational change. In this thesis, this method was applied in predicting the redox potential of cupredoxin protein and investigating the role of electrostatic polarization effect in determination of reduction potential. With increasing extent of polarization effect accounted, the calculated redox potential shift was more accurate comparing with the experimental data. In this thesis, the significance role of electrostatic polarization effect played in molecular dynamics was highlighted. Force fields containing the polarization effect is a way to improve the accuracy of molecular dynamics studies.