Hindawi Publishing Corporation BioMed Research International Volume 2013, Article ID 713585, 12 pages http://dx.doi.org/10.1155/2013/713585 Research Article Improved scFv Anti-HIV-1 p17 Binding Affinity Guided from the Theoretical Calculation of Pairwise Decomposition Energies and Computational Alanine Scanning Panthip Tue-ngeun, 1 Kanchanok Kodchakorn, 1 Piyarat Nimmanpipug, 1,2 Narin Lawan, 1 Sawitree Nangola, 3 Chatchai Tayapiwatana, 4,5 Noorsaadah Abdul Rahman, 6 Sharifuddin Md. Zain, 6 and Vannajan Sanghiran Lee 1,2,6 1 Computational Simulation Modelling Laboratory (CSML), Department of Chemistry and Center of Excellence for Innovation in Chemistry and Materials Science Research Center, Faculty of Science, Chiang Mai University, Chiang Mai 50200, hailand 2 hailand Center of Excellence in Physics, Commission on Higher Education, 328 Sri Ayutthaya Road, Bangkok 10400, hailand 3 Department of Medical Technology, School of Allied Health Sciences, University of Phayao, Phayao 56000, hailand 4 Division of Clinical Immunology, Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, hailand 5 Biomedical Technology Research Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, hailand 6 Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia Correspondence should be addressed to Chatchai Tayapiwatana; asimi002@chiangmai.ac.th and Vannajan Sanghiran Lee; vannajan@gmail.com Received 30 April 2013; Revised 3 September 2013; Accepted 10 September 2013 Academic Editor: Carmen Domene Copyright © 2013 Panthip Tue-ngeun et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Computational approaches have been used to evaluate and deine important residues for protein-protein interactions, especially antigen-antibody complexes. In our previous study, pairwise decomposition of residue interaction energies of single chain Fv with HIV-1 p17 epitope variants has indicated the key speciic residues in the complementary determining regions (CDRs) of scFv anti- p17. In this present investigation in order to determine whether a speciic side chain group of residue in CDRs plays an important role in bioactivity, computational alanine scanning has been applied. Molecular dynamics simulations were done with several complexes of original scFv anti-p17 and scFv anti-p17mutants with HIV-1 p17 epitope variants with a production run up to 10ns. With the combination of pairwise decomposition residue interaction and alanine scanning calculations, the point mutation has been initially selected at the position MET100 to improve the residue binding ainity. he calculated docking interaction energy between a single mutation from methionine to either arginine or glycine has shown the improved binding ainity, contributed from the electrostatic interaction with the negative favorably interaction energy, compared to the wild type. heoretical calculations agreed well with the results from the peptide ELISA results. 1. Introduction One of the challenges in molecular biology consists in impro- ving the structural, functional properties or binding activities of proteins. he antibodies constitute an excellent model to test the potential approaches to this problem because they constitute a homogeneous family of proteins and a large amount of structural and functional data is available. he antigen-binding sites of immunoglobulins are embedded into the variable heavy and light chain domains (V  , V  ) and are specially separated from the efector function-mediating regions located in the Fc fragment. One type of geneti- cally engineered antibody is the single chain Fv fragment (scFv). Single chain Fv fragments are genetically engineered polypeptides that contain a heavy chain variable region (VH)