Rational drug design of smaller chain peptides as cardioprotective agents:
Application towards denovo strategy for drug like properties and docking
studies

K; asamy Nagarajan; Ranjana Ranjan

Abstract

Rational drug design of smaller chain peptides as cardioprotective agents: Application towards denovo strategy for drug like properties and docking studies

Author(s): Kandasamy Nagarajan and Ranjana Ranjan

The main objective of our rational drug design is to predict the best novel shorter chain peptide leads for cardio protective effect from the designed set of templates with various descriptors such as Lipinski rules, molinspiration and swissdock. We built 200 candidate molecules (50 dipeptide,50tripeptide,50 tetrapeptide,50 pentapeptides)and these combination sets were passed through empirical Lipinski filters to assess drug like properties using various molecular descriptors namely molecular mass, hydrogen bond donors, hydrogen bond acceptors, log p(<0.05).The results of Lipinski filters have identified one dipeptide(Leu-Lys),three tripeptides(Ala-Cys-Pro,Gly-Met-Trp,Gly- Trp-Ile)and two tetrapeptides(Ala-Tyr-Phe-Phe,Ala-Cys-Pro-Pro)as potent cardio protective leads. Further ,the selected above 6 peptide leads were subjected to assess drug like properties using molinspiration to check molinspiration property engine,milogp,TPSA,natoms,MW,nviolatios,nrotb,volumerespectively.The results of molinspiration have identified 5 peptide leads with rejection of one tetrapeptide Ala-Tyr-Phe-Phe.In addition ,the same set of leads(5peptides)were subjected to docking with angiotensin converting enzyme target (ACE inhibition)andreceptor target (BETA adrenergic receptor).The calculation of full fitness energy obtained between drug and target receptor/enzyme have shown clearly that the tripeptide Ala-Cys-Pro was more potent with regard to enzyme target having full fitness energy (-538894 k.cal/mol) ,Gly-Trp-Ile was the most potent lead against Betaadrenergic receptor blockade having full fitness energy of (-231766 k.cal/mol).Moreover the dipeptide Leu-Lys and tripeptide Gly-Met-Trp are also identified as potential targets against both enzyme (ACE) and receptor (BETA- 2adrenergic)targets having full fitness energy of (-543953 k.cal/mol) and (-540163 k.cal/mol) against ACE enzyme and (-239715 k.cal/mol) and (-233794 k.cal/mol) against β2 adrenergic target respectively . So we identified 4 compounds Ala-Cys-Pro, Gly-Trp-Ile, Leu-Lys, Gly-Met-Trp as potent peptide leads with maximum conformational stability for cardioprotective effect among the 200 peptide templates

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