Accurately calculating the Gibbs free energies of biomolecules in aqueous phase solution is an important challenge and future goal because most processes take place in aqueous solution. Gibbs free energies give the information about the stability and kinetics of biomolecules which will be helpful in understanding the structure and functions of biomolecules. We have developed a new energy-entropy (EE) method based on multiscale cell correlation (MCC) correction theory which is used to calculated the Gibbs free energy values. Firstly, we applied our MCC theory to calculate the entropy for the range of important industrial liquids modeled with GAFF and OPLS force fields. The calculated entropy values are in good agreement with the experimental values having unsigned errors are 8.7 J Kâ1 molâ1 and 9.8 J Kâ1 molâ1 for GAFF and OPLS force fields respectively. Later we combined our MCC theory with density functional theory (DFT) in quantum mechanics/molecular mechanics (QM/MM) formalism to develop a new EE-MCC method to calculate the Gibbs free energy barriers. We applied our EE-MCC method to calculate the reaction kinetics for the series of nucleophilic substitution reactions where one halogen atom is replaced by a hydroxyl ion in aqueous solution. The calculated Gibbs free energy barriers agree well with experimental and potentials of mean force (PMF) values and with previous computational methods. Furthermore, we applied our EE-MCC method to calculate the binding free energies directly for molecular dynamics (MD) simulations for the series of seven host-guest complexes in SAMPL8 challenge. The EE-MCC binding free energies are found in good agreement with the experiment values giving average unassigned error of 0.9 kcal molâ1. We also studied the chemical reactions which are catalyzed by various non-heme iron enzymes and cytochrome P450 enzymes. To understand the activities of various enzymes we have used either density function theory (DFT), full QM/MM simulations or both of them. For example, the activations of L-arginine (L-Arg) by OrfP and VioC have been studied with active site cluster model techniques. The activations of syringol by the GcoA enzyme have been investigated with the help of computational modeling.
|Date of Award
|1 Aug 2021
- The University of Manchester
|Samuel De Visser (Supervisor) & Richard Henchman (Supervisor)