Molecular modeling technique increase

Molecular modeling techniques can be used to fit novel compounds into the binding site. They need not be structurally similar to the natural substrate but the dominant physiochemical properties should be similar. Modifications can be made to the molecule to improve the fit. This will increase specificity for the target enzyme. Substituents can be added or modified so that regions in the enzyme interact favorably with parts of the inhibitor. Electrostatic interactions, hydrophobicity, and hydrogen-bonding can be included in the fitting process. By judicious choice of substituents, both in vitro and in vivo activity can be optimized. Substituents could be added or modified to... 

On the other hand, molecular modelling techniques have become extremely popular, especially because of increasing computation power. These methods are aimed at calculating the energy of a number of conformations for each molecule at different levels of approximation, and then to study the possible interactions between the molecule and its binding site. It became possible from this approach to describe each molecule/conformation by a series of theoretically computed parameters, some of which are intrinsically 3D in nature. 

Three-dimensional database searching is a powerful new tool for developing novel synthetic targets. This technique can be used in cases where an enzyme/receptor 3-D structure is known, or alternatively in the case where the enzyme/receptor structure is unknown. In the latter case an active compound or series of compounds can be used to develop a pharmacophore model. Because 3-D database searching requires biological data stored in 2-D databases and molecular modelling techniques, we expect to see increased integration of 2-D and 3-D database/ information systems. 

These differences probably contribute to the fact that mathematical modeling is, as yet, not seen as a mainstream research tool in many areas of molecular biology. However, as will be described in the remainder of this chapter, many obstacles in the construction of kinetic models of cellular metabolism can be addressed using a combination of novel and established experimental and computational techniques, enabling the construction of metabolic models of increasing complexity and size. 

Molecular modeling of PT at dense interfacial arrays of protogenic surface groups in PEMs needs ab initio quantum mechanical calculations. In spite of fhe dramafic increase in computational capabilihes, it is still "but a dream" to perform full ab initio calculations of proton and water transport within realistic pores or even porous networks of PEMs. This venture faces two major obstacles structural complexity and the rarity of proton transfer events. The former defines a need for simplified model systems. The latter enforces the use of advanced compufahonal techniques that permit an efficient sampling of rare evenfs. ... 

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