Takayuki Tsukamoto

Three- and four-body corrected fragment molecular orbital calculations with a novel subdividing fragmentation method applicable to structure-based drug design

We develop an inter-fragment interaction energy (IFIE) analysis based on the three- and four-body corrected fragment molecular orbital (FMO3 and FMO4) method to evaluate the interactions of functional group units in structure-based drug design context. The novel subdividing fragmentation method for a ligand (in units of their functional groups) and amino acid residues (in units of their main and side chains) enables us to understand the ligand-binding mechanism in more detail without sacrificing chemical accuracy of the total energy and IFIEs by using the FMO4 method. We perform FMO4 calculations with the second order Møller-Plesset perturbation theory for an estrogen receptor (ER) and the 17β-estradiol (EST) complex using the proposed fragmentation method and assess the interaction for each ligand-binding site by the FMO4-IFIE analysis. When the steroidal EST is divided into two functional units including A ring and D ring, respectively, the FMO4-IFIE analysis reveals their binding affinity with surrounding fragments of the amino acid residues; the A ring of EST has polarization interaction with the main chain of Thr347 and two hydrogen bonds with the side chains of Glu353 and Arg394; the D ring of EST has a hydrogen bond with the side chain of His524. In particular, the CH/π interactions of the A ring of EST with the side chains of Leu387 and Phe404 are easily identified in cooperation with the CHPI program. The FMO4-IFIE analysis using our novel subdividing fragmentation method, which provides higher resolution than the conventional IFIE analysis in units of ligand and each amino acid reside in the framework of two-body approximation, is a useful tool for revealing ligand-binding mechanism and would be applicable to rational drug design such as structure-based drug design and fragment-based drug design.

Locking of passive Q-switched chaotic laser system to small external modulation

complicated phenomena in multimode oscillation, such as spatial pattem formation, optical voltices, chaotic itineracy, spot dancing, synchronization of chaos and etc. Among them, the laser with a saturable absorber (LSA) has revealed various aspects of nonlinear dynamics from a single mode self-sustained regular pulsation to multimode chaotic oscillation. Above all, type-B laser like CO, laser, in which the degree of polarization can be adiabatically eliminated, has a remarkable advantage of describability with rate equation approximation. We have reported5 that regular mode-switching and two distinctive types of chaos exist in a bimode CO, LSA. One type was identified by the period doubling route to chaos and the fractal dimension of the strange attractor was calculated to be 2.02 t0.02. The other was identified by the abrupt transition from the regular oscillation to chaos, where the fractal dimension was calculated to be 2.47 0.01. In this paper we report precisely the route to chaos in the latter case. The dynamics of the bimode CO, LSA system in which one mode is saturably absorbed and the other is free from absorption is described by a set of seven nonlinear rate equations taking the spatial overlap between two modes in a laser gain tube into a c ~ o u n t . ~ Figs. l(a) and (b) show the behavior of peak values of photon densities for both modes as a function of pumping rate. While pumping rate is under threshold level, calculated photon densities show regular single peak pulse train. However, when the pumping rate slightly exceeds the threshold, the peak values start to swing periodically followed by chaotic bursts. The closer the pumping rate is to the threshold, the longer the duration time of unstable but quasi-regular pulsation becomes. Further increase in the pumping rate makes the duration time short and finally the quasiregular pulse train is replaced by chaotic pulses. Such transition from regular pulses to chaos is known as intermittency