Computational protocol: Molecular Basis of ABHD5 Lipolysis Activation

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Protocol publication

[…] Since neither ABHD4 or ABHD5 have experimentally determined 3D structures, we generated a computational model based on homology modeling and shape analysis. We first used psi-blast to iteratively search against PDB to obtain related ABHD protein structures as templates for homology modeling using Modeller. We constructed an ABHD4 model based on soluble epoxide hydrolase (PDB1s8o, 28% sequence identity) and haloalkane dehalogenase (PDB3sk0, 26%) as a template, whereas we obtained an ABHD5 model from a template based on valacyclovir hydrolase (PDB2ocg, 18% sequence identity) and an epoxide hydrolase (PDB1qo7, 14%). Although the pair-wise sequence identity between the epoxide hydrolase template and ABHD5 is less than 15%, the folds of the selected templates from ABHD family members are highly conserved across species. Based on the CATH structural classification, their core structures have been classified into the same fold of 3.40.50.1820 (Alpha Beta 3-Layer aba Sandwich). Both of our initial models for ABHD4 and ABHD5 have a GA341 score of >0.90, indicating that they have high reliability of fold prediction. To further refine our initial models, we conducted MD simulations using GROMACS with ABMBER all-atom force field. Simulations were conducted in explicit solvents and counter ions for 30 nsec after target proteins were solvated and equilibrated in the dynamic equilibrium state. Protein conformers (structures of a target protein at a given time) in a trajectory were then computed for shape analysis of dynamic surfaces and pocket identification. […]

Pipeline specifications

Software tools BLASTP, MODELLER, GROMACS
Application Protein structure analysis
Organisms Homo sapiens
Diseases Neoplasms
Chemicals Amino Acids