Molecular Dynamics Simulation of T4-Lysozyme
Description
Molecular Dynamics Simulation of T4-Lysozyme in the WT and L99A variant
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Molecular dynamics simulations were performed using the AMBER software package. Starting conformation for the L99A were generated by mutating the WT conformation for T4-Lysozyme. For each system, initial coordinates were solvated in a periodic box of explicit water molecules and neutralized by adding counterions (Na+, Cl-) to reach physiological concentration. To ensure proper system stabilization prior to production runs, a rigorous multi-step preparation protocol was employed. Initially, the solvent and ions were minimized while the solute was held in place using harmonic restraints with a force constant of 100 kcal/mol/Å^2. This initial phase consisted of 2,000 minimization cycles (1,000 steps of steepest descent followed by conjugate gradient), deliberately omitting the SHAKE algorithm to allow for the resolution of local steric clashes. Subsequently, the system was gradually heated from 100 K to 298 K in the NVT ensemble over 1 ns (using a 1 fs integration time step), regulated by a Langevin thermostat with a collision frequency of 1.0 ps−1. During the heating phase, a 10 kcal/mol/Å2 restraint was applied to the protein, and the SHAKE algorithm was activated to constrain bonds involving hydrogen atoms. Following heating, the systems were subjected to a comprehensive equilibration phase in the isothermal-isobaric (NPT) ensemble at a reference pressure of 1 atm, controlled by a Monte Carlo barostat. This phase involved the gradual, stepwise release of harmonic restraints on the protein backbone atoms through successive runs of 1 ns, 2 ns, and further cycles totaling approximately 10 ns, progressively reducing the force constant from 10.0 to 0.2 kcal/mol/Å2. Midway through the equilibration protocol, a brief secondary minimization phase (1,000 cycles) was introduced to facilitate side-chain repacking. Production simulations were performed in the NPT ensemble at 300 K using a 2 fs time step. Long-range electrostatic interactions were computed using the Particle Mesh Ewald (PME) method, with a non-bonded interaction cutoff set to 10.0 Å.
Institutions
- University of Milano-BicoccaLombardy, Milan
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Additional Metadata for University of Milano - Bicocca
| Language | English |
| Date the data was collected | 2026-01-14T23:00:00.000Z |
| ERC Keywords | PE1_18 Scientific computing and data processing, PE4_1 Physical chemistry, PE6_13 Bioinformatics, biocomputing, and DNA and molecular computation |
| SSD Classification | CHIM/02 - CHIMICA FISICA |
| Geolocation | Italy |