Understanding the local structure surrounding the site of a protein-drug interaction can provide important insights into the mechanism of the drug and can help inform drug design and repurposing1. While structural information exists for a subset of protein-ligand interactions, it does not cover the space of all experimentally known interactions. As a result, the sites on proteins to which drugs...

This paper gives the details of a web caching architecture which uses ESI and web document fragments to improve the behavior of the web pages from a performance point of view. As the performance of the web page that use fragments depends on the state and parameters fixed in running time, the design of the fragments has to be dynamic and alterable at that phase. The fragment design of web pages ...

The platelet GP Ib-IX receptor supports platelet adhesion and activation by binding to vWf in the exposed subendothelial matrix. An abnormal GP Ib-IX complex exists in platelet-type or pseudo-von Willebrand disease and has a characteristic increased affinity for soluble vWf resulting in impaired hemostatic function due to the removal of larger vWf multimers from the circulation. Genetic studies...

The shape of fragments generated by the breakup of solids is central to a wide variety of problems ranging from the geomorphic evolution of boulders to the accumulation of space debris orbiting Earth. Although the statistics of the mass of fragments has been found to show a universal scaling behavior, the comprehensive characterization of fragment shapes still remained a fundamental challenge. ...

Hit Generation (FBHG) overcomes many of the potential issues and inaccuracies encountered with the traditional approach of high throughput screening (HTS). For example, traditional screening libraries are commonly populated with molecules designed to adhere to Lipinski’s rule of five; however, they tend to be large and lipophilic, making them difficult to develop into potent compounds without c...

Fragment-based drug discovery (FBDD), while still a relatively new approach, has been so successful for identifying ligands for protein targets that it is alreadywidely regarded as representing a sea-change in drug discovery techniques. The strategy involves identifying small (typically ,300Da), low-affinity ligands (‘fragments’) and combining or expanding these to produce larger, higher-affini...

Our constructed ligand efficiency (LE) hot spot surface was used as a guide for structure-based optimization of an AChBP fragment hit. This fragment hit was an analogue of a fragment found in the radioligand binding assay performed on Ls-AChBP, described in Chapter 4. The chemical space around this original fragment was explored by SAR-by-catalogue, thereby increasing its affinity and ligand ef...

Multifragmentation is observed in many reaction types: light ion induced reactions at large incident energies (in the GeV region), central heavy ion collisions from 30 to 100 MeV/u, and peripheral heavy ion collisions between 30 and 1000 MeV/u or above. When nucleus-nucleus collisions are considered, another entrance channel parameter is the corresponding mass asymmetry. The first question whic...