Innovative drug design

Innovative drug design

In silico drug design became widely used in the past dedicate but it was not often employed in the real life, i.e. from the big pharma companies. This has been changed during the last year by the introduction of FEP+ technology by Schrödinger. Many projects are under development now in which most of the big pharmaceutical companies were involved. In this way, many other in silico approaches became also well recognized. The main reason for this progress is the new computation capability and in particular the use of modern GPUs instead CPUs for the calculations, which makes possible an acceleration of about 30-100 times. Unfortunately, although the cosmetics active substance and drug discovery are similar in their initial phase the in silico design is rare used by cosmetics companies.

Our innovative approach includes all modern approaches but also our own innovations. For instance, it is not secret that the initial compounds pose prediction and scoring is very important step and without a good starting conformation all other computational steps may fail. Moreover, it has been recently established that more and more of the drug candidate compounds have a mutable binding modes in a solution. Thus, we have developed a new strategy for both the binding mode and free energy scoring prediction based on the modified accelerated molecular dynamics (aMD). By our approach even the binding constants such as kin and koff can be more easily calculated with help of the computational power of the new GPUs such as Nvidia Pascal P100 Tesla generation. Finally, although the REST method is indeed a good sampling approach and have been already introduced in the FEP calculations the short simulation time suggested guarantee an impressive result mainly for the ligands with very well established binding mode. Because of the fact that the lead optimization is the most expensive step in the drug discovery we combine the FEP approach and the above mentioned our own method to achieve much better results.

Many companies claim that provide in silico drug discovery but a close view of the technologies used shows that only some steps of this complicate process are covered and mainly not well established methods are employed. Instead, we cover all steps by all sophisticated technology available. We can screen a databases with millions chemical compounds and precisely predict the lead drug candidates by many scoring ways. Further, for the lead optimization step the FEP methodology is used but the results are also supposed by our own developments.

Our technology combines but is not limited to following methods:
Docking
Pharmacophore
Scoring by all available advanced functions and methods
Molecular dynamics
Accelerated Molecular dynamics
New core recognizing
Free energy perturbation (FEP)
GPU calculations



DIFFERENCE BETWEEN CLASIC TECHNOLOGY AND OUR INNOVATIVE TECHNOLOGY

Our innovative technology

GPU Power

A graphics processing unit (GPU) in a combination with Compute Unified Device Architecture (CUDA) has provided in the recent few years completely new technology that allows a number of scientific calculations to be massively accelerated.

They provide an access to supercomputer scale performance without waiting for shared resources. GPU accelerators enable computational chemistry and biology researchers to push the boundaries of discovery.

... read more on Computational Chemistry in nvidia.com

Molecular Dynamics

MD simulations reproduce in a realistic way protein behavior in physiological conditions, revealing at a molecular level protein structure and, consequently, protein function.

Notably, this approach is one of the most advanced techniques allowing to differentiate compounds that are capable or not of binding to certain proteins. Nowadays, it is a valuable tool in many areas, including structural biology and in silico drug design.

Molecular Modeling

The field of molecular modeling comprise a vast number of scientific techniques. Docking and Pharmacophore in silico approaches are commonly used in discovery of novel bioactive ligands and in drug design.

By these powerful methods the screening of millions compounds is now possible predicting whether they can bind to certain proteins. Quantum chemistry is a branch of chemistry whose primary focus is the application of quantum mechanics in physical models predicting the chemical structure, physicochemical properties and etc.

Sctructural Biology

Structural biology is a branch of molecular biology, biochemistry, and biophysics concerned with the molecular structure of biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations in their structures affect their function.

Bio Informatics

Bioinformatics is an interdisciplinary field that develops methods and software tools for understanding biological data. As an interdisciplinary field of science, bioinformatics combines computer science, statistics, mathematics, and engineering to study and process biological data.

MICAR21 INNOVATIVE TECHNOLOGY

Our Technology is not just what it looks like and feels like. Technology is how it works revolutionally. - Dimitar Dimitrov