engleski

Search for Allostery in Purine Nucleoside Phosphorylases via Database of Molecular Interactions

Allostery is a phenomenon where the information is transmitted from one part of the enzyme to the other. The means by which this is achieved is still to be understood in many proteins. One class of enzymes where allostery plays an intriguing role are Purine Nucleoside Phosphorylases (PNPs) [1]. Since allostery is a fundamentally dynamical phenomenon, the static structures provided by X- ray crystallography only are not able to reveal it. It is necessary to somehow include the dynamics by leveraging the molecular dynamics simulations. Adding a time dimension in form of molecular simulations to the static picture is essential for following the changes in molecular contacts and tracing the signatures of allosteric communication between different parts of the protein. To facilitate the information retrieval from this complex data, specially designed molecular interaction databases have been applied in search for allosteric pathways in PNPs, as part of the project Allosteric communication pathways in oligomeric enzymes (ALOKOMP, https://alokomp.irb.hr/). By enhancing the static information obtained from X-ray crystallography with dynamic time evolution obtained via molecular dynamics simulations and combining both in form of specially designed databases to which automated machine learning algorithms can be applied, it is hoped that elusive allosteric pathways can be identified in this class of enzymes.

allostery ; purine nucleoside phosphorylases ;

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