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Among the many applications of molecular modeling, drug design is probably the one with the highest demands on the accuracy of the underlying structures. During lead optimization, the position of every atom in the binding site should ideally be known with high precision to identify those chemical modifications that are most likely to increase drug affinity. Unfortunately, X-ray crystallography at common resolution yields an electron density map that is too coarse, since the chemical elements and their protonation states cannot be fully resolved.This chapter describes the steps required to fill in the missing knowledge, by devising an algorithm that can detect and resolve the ambiguities. First, the pK (a) values of acidic and basic groups are predicted. Second, their potential protonation states are determined, including all permutations (considering for example protons that can jump between the oxygens of a phosphate group). Third, those groups of atoms are identified that can adopt alternative but indistinguishable conformations with essentially the same electron density. Fourth, potential hydrogen bond donors and acceptors are located. Finally, all these data are combined in a single "configuration energy function," whose global minimum is found with the SCWRL algorithm, which employs dead-end elimination and graph theory. As a result, one obtains a complete model of the protein and its bound ligand, with ambiguous groups rotated to the best orientation and with protonation states assigned considering the current pH and the H-bonding network. An implementation of the algorithm has been available since 2008 as part of the YASARA modeling & simulation program.

SynopsisThe rate of product formation as well as detailed product composition were measured in the rapid pyrolysis of a 1.3-cm cylindrical pellet of lignin, a major component of biomass. Volume heating by dielectric-loss microwave heating resulted in rapid weight loss with an apparent rate coefficient of 1-5 min-'. Char yield was surprisingly low (33%) owing to the rapid heating rate and high temperature of the pellet. Total gas yield was 38%, of which 12% were simple hydrocarbons and Hz (both weight percent, of original lignin). Product composition showed extensive secondary reaction a t high temperatures evidenced by the significant yields of CzH2, Hz, and condensed aromatics as well as the typical lignin cracking products such as phenols. Poor coupling of microwave energy to lignin required large power settings in order t o initiate reaction. Once initiated, the reaction rate was difficult to control because of the exothermic nature of the reactions. Additives of a suitable composition to increase coupling may be a possible solution to this problem and may result in more favorable economics.

SynopsisThe pyrolysis of organic waste polymers to produce fuels and chemicals is of interest to augment petroleum-based processes. The wide variety of pyrolysis products of low yield and the uncertain role that heat transfer rate plays in determining these have been deterrents to utilization in the past. A possible approach to increased selectivity for products is to heat them rapidly and homogeneously with the aim of narrowing the product distribution. A very rapid means of homogeneous heat transfer throughout the substrate is microwave heating. A laboratory study has been done to determine what effect high-intensity microwave energy has on the thermal degradative pathways of cellulose. The product distribution found when cellulose is pyrolyzed in the absence of a microwave discharge is similar to that found in conventional furnace pyrolysis. The major products are levoglucosan (27%), carbon dioxide (2-5%), water, and charred residue. However, the total heat-up and reaction times for even large pellets are reduced to less than 2-3 min when high-intensity microwave irradiation is employed, Effects of pressure and microwave power are reported. Low external gas temperature also prevents secondary reactions.

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