Molecular dynamics simulations of lipases Review International Journal of Integrative Biology A journal for biology beyond borders ISSN 0973-8363 Molecular dynamics simulations of lipases Kaushik Ramakrishnan S, Vinatha Krishna, Vinod Kumar KS, Lakshmi BS, Sharmila Anishetty, Pennathur Gautam * Centre for Biotechnology, Anna University, Chennai, India Submitted: 2 Apr. 2008; Accepted: 17 May 2008 Abstract Molecular dynamics simulation of lipase movements have revealed the structural aspects of the protein responsible for interfacial activation, varying activity at different pH and domain movements responsible for activity. A lid domain is implicated in the interfacial activation of lipases and recently a second lid has been discovered in Pseudomonas aeruginosa lipase using dynamic simulations of the crystal structure.. Rhizomucor miehei lipase despite changing its global conformation in the presence of cyclohexane was able to retain its active site conformation and hence activity. Experimental proof of Candida rugosa's preference for hydrophobic solvents was corroborated using simulation and visualization of lid movements in the presence of various solvents. Molecular dynamics simulations provide a versatile tool for exploring structure-function relationships and in conjunction with other computational techniques like molecular modeling and in-silico mutations will lead the way to engineering enzymes for enhanced functions in desired conditions. Keywords: Molecular dynamics, simulation, lipase, domain, movement. INTRODUCTION INTRODUCTION Revealing the biological function of proteins apart from resolving structures, involves understanding the chemical interactions and properties such as solubility and degree of ionisation. Structures of several enzymes, mutants and substrate inhibitor complexes have been solved and deposited in the Protein data bank (Berman et al., 2000). This wealth of information along with the need to quickly and precisely characterise them has led to in-silico approaches using modelling, docking and dynamic simulation since In-vitro studies alone cannot reveal molecular mechanism. (Sotomayer et al., 2007). Revealing the biological function of proteins apart from resolving structures, involves understanding the chemical interactions and properties such as solubility and degree of ionisation. Structures of several enzymes, mutants and substrate inhibitor complexes have been solved and deposited in the Protein data bank (Berman et al., 2000). This wealth of information along with the need to quickly and precisely characterise them has led to in-silico approaches using modelling, docking and dynamic simulation since In-vitro studies alone cannot reveal molecular mechanism. (Sotomayer et al., 2007). Lipases (3.1.1.3) are ubiquitous enzymes found in microbes (Gilbert, 1993; Jaeger et al., 1994 and 1999), plants (Mukherjee et al., 1994) and animals (Carriere et al., 1994; Chapus et al., 1988) .They are triacylglycerol hydrolases that catalyze both the hydrolysis and synthesis of long chain triacylglycerols. Specificity of lipase catalyzed reactions have been known for long (Desnuelle et al., 1963; Klein et al., 1997), as also their ability to work in organic solvents (Almarsson et al., 1995; Klibanov, 1986; Fitzpatrick et al., 1993) enantioselectivity (Dakin, 1903) and interfacial activation (Brzozowski et al., 1991).They are industrially important enzymes catalyzing a variety of synthetic reactions and have been used for the preparation of optically pure compounds in pharmaceutical industry. They are also used widely in detergent (Wolff et al., 1997) and food industries (Gupta et al., 2003; Willis et al., 1998). Lipases (3.1.1.3) are ubiquitous enzymes found in microbes (Gilbert, 1993; Jaeger et al., 1994 and 1999), plants (Mukherjee et al., 1994) and animals (Carriere et al., 1994; Chapus et al., 1988) .They are triacylglycerol hydrolases that catalyze both the hydrolysis and synthesis of long chain triacylglycerols. Specificity of lipase catalyzed reactions have been known for long (Desnuelle et al., 1963; Klein et al., 1997), as also their ability to work in organic solvents (Almarsson et al., 1995; Klibanov, 1986; Fitzpatrick et al., 1993) enantioselectivity (Dakin, 1903) and interfacial activation (Brzozowski et al., 1991).They are industrially important enzymes catalyzing a variety of synthetic reactions and have been used for the preparation of optically pure compounds in pharmaceutical industry. They are also used widely in detergent (Wolff et al., 1997) and food industries (Gupta et al., 2003; Willis et al., 1998). Extensive Molecular Dynamics studies of solvent temperature and pH effects on lipase activity has enabled us to corroborate and increase the understanding of their molecular motion (Peters GH et al., 1996; Peters GH, 2002; Cherukuvada et al., 2005; James et al., 2007) and catalytic site architecture(Lakshmi et al., 1999; Lakshmi et al., 2000). Molecular dynamics provides us the flexibility to model different systems, reaction conditions and most importantly mutations simulating classical or Extensive Molecular Dynamics studies of solvent temperature and pH effects on lipase activity has enabled us to corroborate and increase the understanding of their molecular motion (Peters GH et al., 1996; Peters GH, 2002; Cherukuvada et al., 2005; James et al., 2007) and catalytic site architecture(Lakshmi et al., 1999; Lakshmi et al., 2000). Molecular dynamics provides us the flexibility to model different systems, reaction conditions and most importantly mutations simulating classical or * Corresponding author: Pennathur Gautam, Ph.D. Centre for Biotechnology Anna University, Guindy Campus Chennai 600025, India Email: pgautam@annauniv.edu International Journal of Integrative Biology IJIB, 2008, Vol. 2, No. 3, 204 © IJIB, All rights reserved