Molecular dynamics simulations identify the regions of compromised thermostability in SazCA

Abstract

The present study examined the structure and dynamics of the most active and thermostable carbonic anhydrase, SazCA, probed using molecular dynamics simulations. The molecular system was described by widely used biological force‐fields (AMBER, CHARMM22, CHARMM36, and OPLS‐AA) in conjunction with TIP3P water model. The comparison of molecular dynamics simulation results suggested AMBER to be a suitable choice to describe the structure and dynamics of SazCA. In addition to this, we also addressed the effect of temperature on the stability of SazCA. We performed molecular dynamics simulations at 313, 333, 353, 373, and 393 K to study the relationship between thermostability and flexibility in SazCA. The amino acid residues VAL98, ASN99, GLY100, LYS101, GLU145, and HIS207 were identified as the most flexible residues from root‐mean‐square fluctuations. The salt bridge analysis showed that ion‐pairs ASP113‐LYS81, ASP115‐LYS81, ASP115‐LYS114, GLU144‐LYS143, and GLU144‐LYS206, were responsible for the compromised thermal stability of SazCA.

Kinetic Modeling, Thermodynamic Approach and Molecular Dynamics Simulation of Thermal Inactivation of Lipases from Burkholderia cepacia and Rhizomucor miehei

“…It was found that the RMSD of the 3LIP ( B. cepacia lipase) and 3TGL ( R. miehei lipase) was 0.77 ± 0.26 Å and 0.84 ± 0.26 Å at 313 K, and 0.84 ± 0.24 Å and 0.92 ± 0.31 Å at 343 K, respectively. Considering that the RMSD change below 2.5 Å is an indicator of no significant conformational changes in protein structure [ 75 ], and a low RMSD indicates that the protein is stable during the simulation time [ 76 ], the RMSD results for both lipases showed that increasing the temperature to 343 K did not cause great structural differences.…”

“…The number of hydrogen bonds decreased for both lipases with an increase in the temperature from 313 to 343 K. The loss of hydrogen bonds at 70 °C for 3TGL and 3LIP was 15 and 20%, respectively ( Table 5 ). In general, the lesser the number of hydrogen bonds, the higher the flexibility of the protein and the lower its thermostability [ 76 ]. Taking into account that lipase from R. miehei has a lower number of hydrogen bonds at 313 K than that of bacterial origin, the additional loss of hydrogen bonds at 343 K can be related to the slight increase in flexibility ( Figure 5 B) and its lower thermal stability.…”

Structural Consequence of Non-Synonymous Single-Nucleotide Variants in the N-Terminal Domain of LIS1

“…F31S remains unchanged in terms of SASA compared to wild-type. The Rg analysis indicates protein compactness, while SASA denotes the change in the solvent-accessible area, which accounts for protein folding stability [ 48 ]. Cumulatively, these analyses, such as RMSD, Rg, and SASA, direct that variants containing structures confer a substantial conformational alteration in the LIS1 structure, which might involve conformational deviations in the nearby areas around the variant location.…”

Enzyme–substrate interactions in orotate-mimetic OPRT inhibitor complexes: a QM/MM analysis

“…In this study, we assessed the relative contribution of strong and weak hydrogen bonds in OA and OA-mimetic inhibitors at protein-ligand interfaces because hydrogen bonds have been reported to facilitate ligand binding, protein-ligand selectivity and protein folding. 32,[34][35][36] We applied a geometrical criterion to identify the hydrogen bonds. A cutoff distance between the hydrogen-bond-donor and the acceptor was employed to classify strong and weak hydrogen bonds.…”