Fragmental Methods in the Design of New Compounds. Applications of The Advanced Algorithm Builder

Abstract

Fragmental methods (FMs) have great potential in many practical areas related to the design of new lead compounds. Advanced Algorithm Builder TM (AAB) is a new software system which employs FMs in (i) building QSPR, QSAR and SAR models, (ii) converting them to custom (in-house) algorithms and screening filters, and (iii) predicting physical properties and biological activities for new compounds. This review demonstrates how FMs and AAB can be used to substantiate our intuition, interpret observations, validate hypotheses and obtain new algorithms for predicting physical properties and biological activities. Applications for practical and theoretical chemists in the design of new lead compounds are discussed.

It Is Important to Compute Intramolecular Hydrogen Bonding in Drug Design?

“…Japertas et al [262] reported a fragment-based method while a more rigorous method based on quantum mechanics calculations has been described by Gancia et al [263] The latter method was based on the premise that Abraham's H-bond scales could be related to parameters derivable from quantum-mechanical calculations such as atom self-polarizability and electrophilic superdelocalizability. These are, broadly speaking, parameters that include terms relating to the degree to which a given molecular orbital receives a contribution from an atomic orbital, and the energy of the orbital.…”

Trainable structure–activity relationship model for virtual screening of CYP3A4 inhibition

“…Molecule fragmentation and all subsequent statistical analysis were performed using Algorithm Builder 1.8 software [35,36], except SVM and Random Forest models which were developed using R 2.6.2 [37]. ROC curves were generated by a web-based calculator [38].…”

P-Dimethylaminobenzaldehyde semicarbazone: The bonding abilities of imine nitrogen atom

“…It is believed that the biological activity is related to the lipophilicity, thus the 1-octanol/water partition coefficient [43][44][45][46][47][48][49][50] and molecular polar surface area (PSA) [51] of compound were calculated. The values of average log P equal to 1.31 (22) and PSA equal to 70.72 Å 2 suggest the concept that the compound can be transported via biological membranes to binding site.…”