Protein flexibility in psychrophilic and mesophilic trypsins. Evidence of evolutionary conservation of protein dynamics in trypsin‐like serine‐proteases

Abstract

To shed light on the molecular features related to cold-adaptation in serine-proteases, we have carried out molecular dynamics simulations of homologous mesophilic and psychrophilic trypsins, with particular attention to evaluation of intramolecular interactions and flexibility.Psychrophilic trypsins present fewer interdomain interactions and enhanced localized flexibility in regions close to the catalytic site. Notably, these regions fit well with the pattern of protein flexibility previously reported for psychrophilic elastases. Our results indicate that specific sites within the serine-protease fold can be considered hot spots of cold-adaptation and that psychrophilic trypsins and elastases have independently discovered similar molecular strategies to optimize flexibility at low temperatures.

Free-energy landscape, principal component analysis, and structural clustering to identify representative conformations from molecular dynamics simulations: The myoglobin case

“…Further details on the MD setup and solvent equilibration, termalization and pressurization steps are reported in ref. [41].…”

Molecular motions and free-energy landscape of serine proteinase K in relation to its cold-adaptation: a comparative molecular dynamics simulation study and the underlying mechanisms

“…In recent years, many studies have focused on the relationship between the structure and function of psychrophilic enzymes and the coldadaptation of psychrophiles. [10][11][12][13][14][15][16] A general theory for coldadaptation has not been formulated. However, psychrophilic enzymes are oen characterized by enhanced exibility at low temperatures to obtain higher catalytic efficiency (k cat /K m ) and to cope with the reduction of metabolic uxes and chemical reaction rates.…”

Molecular dynamics investigation of cyclic natriuretic peptides: Dynamic properties reflect peptide activity

“…Moreover, backbone flexibility profiles diverge slowly, being conserved both at family and superfamily levels [50][51][52]. A recent study, in the context of cold adaptation, has shown that warm-and cold-adapted enzymes belonging to the same family present common dynamics signature related to the same fold but also peculiar differences which may reflect temperature adaptation [53].…”