Vol.:(0123456789) 1 3 Molecular Biology Reports https://doi.org/10.1007/s11033-018-4308-3 ORIGINAL ARTICLE Molecular dynamics simulation as a tool for assessment of drug binding property of human serum albumin Meenu Narwal 1  · Deepak Kumar 2  · Tapan Kumar Mukherjee 1  · Rajasri Bhattacharyya 2  · Dibyajyoti Banerjee 2 Received: 4 June 2018 / Accepted: 10 August 2018 © Springer Nature B.V. 2018 Abstract Human serum albumin (HSA) is a major plasma protein and binding of drugs with this plasma protein has a great importance. It possess esterase activity which can cleave the drugs containing ester bond and thus, can regulate the efect of drugs. Till date no systematic study has been done to analyse binding of such drugs and to compare the results with the drugs which do not have ester bond. Therefore, in the present study two diferent categories—ester and non-ester drugs have been considered to analyse their interaction with HSA at two principle drug binding sites using molecular modelling tools. It is observed that the drugs irrespective of ester or non-ester nature prefer either Sudlow site I or II by hydrogen bond and hydrophobic interactions. The information obtained from the study can assist to study pharmacokinetics of the drugs and that in turn will help in noval drug discoveries. Keywords HSA · Ester drug · Non-ester drug · Drug–HSA interaction · Esterase activity Abbreviations HSA Human serum albumin MD Molecular dynamics Rg Radius of gyration RMSD Root mean square deviation Introduction The interaction of drugs with human serum albumin (HSA) has been a feld of enormous research from decades. The efectiveness of drugs as pharmaceutical agents depends on their binding afnity. HSA is an essential carrier protein for drugs in human plasma [1]. It serves to transport drugs and other metabolites to their target tissues. Also, HSA is a major plasma protein and has well known structure [2, 3].Also, it has esterase activity which have been reported earlier and this activity can cleave the ester bond by hydroly- sis [4, 5]. Many researches have reported presence of two major drug binding sites on HSA termed as Sudlow site I and Sudlow site II [6, 7]. Binding of drugs like warfa- rin, halothane, propofol and ibuprofen at Sudlow site I and Sudlow site II is well known [8–11]. The information about binding of drugs is crucial as it has direct correlation with drug delivery, pharmacokinetic, pharmacodynamics and therapeutic efcacy [12–14]. Thus, it is essential to study binding for designing and development of new drugs. In the present study, we aim to study about interaction of HSA with two diferent classes of drugs termed as ester drugs (containing ester bond in their structure) and non-ester drugs (do not contain ester bond in their structure). Ester drugs may be cleaved by pseudoesterase activity of HSA. Consid- ering such enzymatic action of HSA we have studied both ester and non ester drugs [4, 5]. Many drugs considered in the present study are already available in the market but their interaction with HSA is not known till date which is an essential aspect as it is the major plasma protein in humans. The study was carried out by using in silico methods to gain useful insight about how binding of drugs is regulated and whether the structure or nature plays an important role in binding, signifcance of binding and the efect of binding on overall distribution and their mechanism so that this infor- mation can be utilized for new pharmaceutical discoveries. * Rajasri Bhattacharyya bdr.rajasri@yahoo.in * Dibyajyoti Banerjee dibyajyoti5200@yahoo.co.in 1 Department of Biotechnology, Maharishi Markandeshwar University, Mullana, Ambala, Haryana 133203, India 2 Department of Experimental Medicine and Biotechnology, PGIMER, Chandigarh 160012, India