Application Of The EIIP/ISM Bioinformatics Concept in Development of New Drugs

Abstract

The development of a new therapeutic drug is a complex, lengthy and expensive process. On average, only one out of 10,000 - 30,000 originally synthesized compounds will clear all the hurdles on the way to becoming a commercially available drug. The process of early and full preclinical discovery and clinical development for a new drug can take twelve to fifteen years to complete, and cost approximately 800 million dollars. The field of bioinformatics has become a major part of the drug discovery pipeline playing a key role in improvement and acceleration of this time and money consuming process. Here we reviewed the application of the EIIP/ISM bioinformatics concept for the development of new drugs. This approach, connecting the electron-ion interaction potential of organic molecules and their biological properties, can significantly reduce development time through (i) identification of promising lead compounds that have some activity against a disease by fast virtual screening of the large molecular libraries, (ii) refinement of selected lead compounds in order to increase their biological activity, and (iii) identification of domains of proteins and nucleotide sequences representing potential targets for therapy. Special attention is paid in this review to the application of the EIIP/ISM bioinformatics platform along with other experimental techniques (screening of a phage displayed peptide libraries, testing selected peptides and small molecules for antiviral activity in vitro) in development of HIV entry inhibitors, representing a new generation of the AIDS drugs.

Structural and Functional Modeling of Artificial Bioactive Proteins

“…the protein virtual spectroscopy technique, i.e., the informational spectrum method (ISM), based on the amino acid electron-ion interaction potential (EIIP) [40][41][42][43][44]; 2.…”

“…From a practical standpoint, it would be desirable not only to construct and test a large number of structural patterns in proteins, but also to predict the functional characteristics of the newly-designed molecules. To address this problem, we analyzed 15 SynRescue protein sequences using the informational spectrum method (ISM) [40][41][42][43][44]. This is a virtual spectroscopy method for structure-function analysis of proteins based on the amino acid electron-ion interaction potential (EIIP) in the Rydberg energy units [40][41][42][43][44].…”

“…To address this problem, we analyzed 15 SynRescue protein sequences using the informational spectrum method (ISM) [40][41][42][43][44]. This is a virtual spectroscopy method for structure-function analysis of proteins based on the amino acid electron-ion interaction potential (EIIP) in the Rydberg energy units [40][41][42][43][44]. According to the underlying theory, the highest peaks found using this type of analysis represent hot spots, i.e., bioactive parts, of the protein molecule [40][41][42][43][44].…”

“…This is a virtual spectroscopy method for structure-function analysis of proteins based on the amino acid electron-ion interaction potential (EIIP) in the Rydberg energy units [40][41][42][43][44]. According to the underlying theory, the highest peaks found using this type of analysis represent hot spots, i.e., bioactive parts, of the protein molecule [40][41][42][43][44]. Table 2 presents the results of virtual spectroscopy for seven Hecht_α SynRescue proteins that save Escherichia coli auxotrophs with disrupted amino acid enzyme pathways for serine (SerB), glutamate/glutamic acid (GltA) and isoleucine (IlvA).…”

“…This virtual spectroscopy method is useful for structure/function analysis of proteins and the identification of functional protein domains [40][41][42][43][44]. The method is also applicable for the assessment of biological effects of mutations.…”