ORIGINAL RESEARCH Applying ultra-accelerated quantum chemical molecular dynamics technique for the evaluation of ligand protein interactions Kamlesh Kumar Sahu Æ Mohamed Ismael Æ Shah Md. Abdur Rauf Æ Ai Suzuki Æ Riadh Sahnoun Æ Michihisa Koyama Æ Hideyuki Tsuboi Æ Nozomu Hatakeyama Æ Akira Endou Æ Hiromitsu Takaba Æ Ramesh Chandra Deka Æ Carlos A. Del Carpio Æ Momoji Kubo Æ Akira Miyamoto Received: 27 September 2008 / Accepted: 6 February 2009 / Published online: 11 March 2009 Ó Birkha ¨user Boston 2009 Abstract Ligand–protein interactions have been studied using several chemical information techniques including quantum chemical methods that are applied to truncated systems composed of the ligand molecule and the surrounding amino acids of the receptor. Fragmented quantum molecular chemical studies are also a choice to study the enzyme–ligand system holistically, however there are still restrictions on the number of water molecules that can be included in a study of this nature. In this work we adopt a completely different approach to study ligand– protein interactions accounting explicitly for as many solvent molecules as possible and without the need for a fragmented calculation. Furthermore, we embed our quantum chemical calculations within a molecular dynamics framework that enables a fundamentally fast system for quantum chemical molecular dynamic simulations (QCMD). Central to this new system for QCMD is the tight binding QC system, newly developed in our laboratories, which combined with the MD para- digm results in an ultra-accelerated QCMD method for protein–ligand interaction evaluations. We have applied our newly developed system to the dihydrofolate K. K. Sahu (&)  M. Ismael  S. Md. A. Rauf  R. Sahnoun  M. Koyama  H. Tsuboi  N. Hatakeyama  A. Endou  H. Takaba  C. A. Del Carpio  A. Miyamoto Department of Applied Chemistry, Graduate School of Engineering, Tohoku University, Sendai, Japan e-mail: kamleshsemail@yahoo.co.in A. Suzuki  R. C. Deka  A. Miyamoto New Industry Creation Hatchery Center, Tohoku University, Sendai, Japan M. Kubo Fracture and Reliability Research Institute, Graduate School of Engineering, Tohoku University, Sendai, Japan Med Chem Res (2010) 19:1–10 DOI 10.1007/s00044-009-9167-y MEDICINAL CHEMISTR Y RESEARCH