A Bioinformatics Method for the Production of Antibody-Drug Conjugates Through Site-Specific Cysteine Conjugation

Antibody-drug conjugates (ADCs) have emerged as a promising class of targeted anticancer therapy, and it is distinguished from traditional chemotherapeutic approaches by its potential to kill cancer cells with limited side effects. Site-specific conjugation is one of the current challenges in ADC development because it allows for controlled conjugation and production of homogeneous ADCs. This chapter describes a computational method for the generation of antibody-drug conjugates as PDB files through site-specific cysteine conjugation, given the PDB files of a drug, a linker, and an antibody. The drug and linker are reconfigured using the rotation and translation functions of an affine transformation, which is brought in appropriate positions for the bonds to occur between the three molecules. The hydrogen and disulfide bonds are employed to connect the linker and drug as well as the linker with the antibody, respectively. Examples of conjugates produced with the presented method have been demonstrated

Molecular dynamics simulations through GPU video games technologies

Bioinformatics is the scientific field that focuses on the application of computer technology to the management of biological information. Over the years, bioinformatics applications have been used to store, process and integrate biological and genetic information, using a wide range of methodologies. One of the most de novo techniques used to understand the physical movements of atoms and molecules is molecular dynamics (MD). MD is an in silico method to simulate the physical motions of atoms and molecules under certain conditions. This has become a state strategic technique and now plays a key role in many areas of exact sciences, such as chemistry, biology, physics and medicine. Due to their complexity, MD calculations could require enormous amounts of computer memory and time and therefore their execution has been a big problem. Despite the huge computational cost, molecular dynamics have been implemented using traditional computers with a central memory unit (CPU). A graphics processing unit (GPU) computing technology was first designed with the goal to improve video games, by rapidly creating and displaying images in a frame buffer such as screens. The hybrid GPU-CPU implementation, combined with parallel computing is a novel technology to perform a wide range of calculations. GPUs have been proposed and used to accelerate many scientific computations including MD simulations. Herein, we describe the new methodologies developed initially as video games and how they are now applied in MD simulations