An accurate estimation of binding free energy between protein and ligand, is one of the most important issues in the drug discovery process. However, it is an arduous and hard process to obtain accurate energy, especially the experimentally relevant free energies for protein-ligand in solution, including a proper treatment of the long-range electrostatics and solvation effects that are involved in optimization of atomic net charges and so on. In this study, the impacts of the various atomic net charge models were considered, and their effects on binding free energy profiles also were investigated. The methods were tested on: the 30 structurally diverse ligands of diverse protein complexes, the 14 structurally diverse ligands of the protein kinase B (PKB) and the 10 structurally diverse ligands of the cyclin-dependent kinases 2 (CDK2) with measured affinities. The tested charges were calculated based on AM1 (Austin Method, version 1) - BCC (bond charge correction), MNDO (modified neglect of diatomic differential overlay), PM5 (Parameterisation Model, version 5), MUL (Mulliken), CM2 (Charge Model 2), CM3 (Charge Model 3), RESP (restrained electrostatic potential) and QM/MM (quantum mechanics/molecular mechanics) models. Our findings showed that the MNDO charge model was best propitious for PKB system and QM/MM for CDK2, whereas none of any given models was suited for the diverse ligands of diverse protein complexes. The trends of MM-PBSA binding free energies using all charge models were in good accord with experimental results for CDK2 but not for PKB in most cases. Considering the above results, particular attention should be paid to the ligand-charge and maybe protein-charge during the estimation of accurate binding free energies in drug design.

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Laser-induced reactions of Ge(111), Si(111), GaAs(100), and InP(100) surfaces with chlorine under 355-, 560-, and 1064-nm laser irradiation have been investigated using a supersonic beam technique and time-resolved mass spectrometry. It has been found that the reaction yields depend not only on the laser fluence and wavelength, but also on the translational energy of the incident chlorine molecules. A possible mechanism of laser-induced reactions is proposed.

Laser-induced chemical reaction of semiconductor with halogen and halogen compounds has attracted much attention in recent years due to its potential application in fabrication of microelectronic devices. We have reported UV and visible laser-induced reactions of Si and GaAs surfaces with chlorine using a CW molecular beam technique coupled with time-resolved mass spectrometry(1,2,). This paper will present recent studies in our laboratory on laser-induced reactions of Ge(111), Si(111), GaAs(100) and lnP(100) surfaces with chlorine molecules under 355-, 560-, and 1064-nm laser irradiations. We are particularly interested in the use of near infrared (1064-nm) laser photons as well as the promotion of reaction by raising the incident chlorine molecules’ translational energy. The objective is to achieve a better understanding of the mechanism of laser-induced reaction and its potential application in the chemical etching of semiconductor.