Computer modelling for fitting possible structures to diffraction data

Modern structural biology is a combination of diffraction experiments using X-rays or electron, and computer simulation for fitting possible structures to the diffraction data.   Specifically, after protein crystallization and determination of structure through X-ray diffraction or cryo-electron microscopy, the resulting data remains difficult to understand. Thus, molecular simulation tools such as molecular dynamics are … More Computer modelling for fitting possible structures to diffraction data

Utility of molecular simulation in constraining possible mechanisms of macroscopic phenomenon

Molecular mechanisms underpin macroscopic phenomenon that we observe, but inability to visualize microscopic events for determining the mechanisms involved precluded scientists from pinpointing the exact mechanistic details of a phenomenon. However, contemporary molecular simulation tools and techniques such as molecular dynamics have attained the temporal and spatial resolution for informing possible mechanistic details of events … More Utility of molecular simulation in constraining possible mechanisms of macroscopic phenomenon

Inability to achieve atomic resolution structure for molecular complexes such as ribosome through molecular dynamics simulation

Contemporary state-of-the-art structure elucidation studies typically employ molecular dynamics simulation to provide an atomistic view of the molecules under study. While useful in providing guidance to the potential structural conformation space available to the molecule, molecular dynamics data remains an educated guess of the true conformations of the molecules. More importantly, atomistic molecular dynamics simulations … More Inability to achieve atomic resolution structure for molecular complexes such as ribosome through molecular dynamics simulation

Cryo electron microscopy’s increasingly important role in structural biology

Cryo electron microscopy has been increasingly used in determining the structure of biomolecules such as proteins down to the atomic resolution level of 2 to 4 Angstrom. More importantly, capable of determining the native structure of proteins in frozen solutions, the method is finding increasing use in protein structure elucidation. Specifically, cryo electron microscopy find … More Cryo electron microscopy’s increasingly important role in structural biology

Obtaining movies of molecular movement of proteins through serial femtosecond crystallography

Seeing is believing; thus, it would be much better if we could observe real-time molecular level movement of proteins during catalysis, where, for example, binding of a substrate to an active site leads to molecular cleavage and enzymatic action. But, this feat is not realized until recent advent of serial femtosecond crystallography (SFX).   In … More Obtaining movies of molecular movement of proteins through serial femtosecond crystallography

Structural impediments to synthesis of bacterial cell wall

Article in Nature, Vol. 533, Issue 7604, pp. 557-560, “Structural insights into inhibition of lipid I production in bacterial cell wall synthesis”   Summary of article: Using X-ray diffraction, isothermal titration calorimetry and modelling, modes of binding and conformational rearrangement induced by binding of a synthesized inhibitor into a glycosyl transferase class enzyme was studied, … More Structural impediments to synthesis of bacterial cell wall

Architecture of multienzyme complex in action: polyketide synthase

Article in Nature, Vol. 531, 24 March 2016, pp. 533, “Mycocerosic acid synthase exemplifies the architecture of reducing polyketide synthases”   Summary of article: Various domains of polyketide synthases were crystallized individually or as segments, and the overall structure of the enzyme complex elucidated. While the method used structures of individual subunits to reconstruct the … More Architecture of multienzyme complex in action: polyketide synthase

The arduous process of drug discovery and development

Drug development is a continuous process. Specifically, there will always be drugs in preclinical development and more advanced ones in clinical trials. These medicines are typically exorbitant in cost due to a variety of reasons, the most important of which is their small production volume coupled with the need to recoup the hefty investment needed … More The arduous process of drug discovery and development

Elucidating molecular processes of molecules in dilute solutions with X-ray free electron laser spectroscopy

With diffraction quality crystals a rarity and some compounds and proteins almost impossible to crystallize, or in a crystal form without ligand in binding cavity, structural biology is often thought of as a field for the most patient. Why? Notwithstanding whether a particular target protein would form crystals of quality sufficient for structural elucidation, some … More Elucidating molecular processes of molecules in dilute solutions with X-ray free electron laser spectroscopy

Combining different experiment and instrument approaches to reconstruct how a protein moves and function

Structural biology is a field in biology research that seeks to understand the role of structure in potentiating function of an enzyme, receptor, or intracellular effector. To do that, it needs to first obtain the structure of the biomolecule of interest through either the gold standard X-ray diffraction technique or the more recent method of … More Combining different experiment and instrument approaches to reconstruct how a protein moves and function