An investigation into how lipids diffuse in the presence of varying protein:lipid number ratios reveals that protein crowding results in drastically different lipid and protein diffusion due to the strengthened impact of correlated motion.

https://link.aps.org/pdf/10.1103/PhysRevX.6.021006

Protein Crowding in Lipid Bilayers Gives Rise to Non-Gaussian Anomalous Lateral Diffusion of Phospholipids and Proteins

This review gives an overview of the key results in various fields of membrane technology with special emphasis to their exploitation in sustainable industrial applications. Considerable progress has been made in short time in a number of important application areas: membrane technology and engineering for water treatment, gas separation, purification and recovery in petrochemical, chemical, pharmaceutical, electronic industry, regenerative medicine etc. The basic properties of membrane operations (generally a-thermal; simple in concept and operation; modular and easy to scale-up; with a potential for more rational utilization of raw materials and recovery and reuse; compatible to a retrofit strategy) are at the basis of their integration into industrial practice.

Membrane processes for a sustainable industrial growth

The effects of crowding in biological environments on biomolecular structure, dynamics, and function remain not well understood. Computer simulations of atomistic models of concentrated peptide and protein systems at different levels of complexity are beginning to provide new insights. Crowding, weak interactions with other macromolecules and metabolites, and altered solvent properties within cellular environments appear to remodel the energy landscape of peptides and proteins in significant ways including the possibility of native state destabilization. Crowding is also seen to affect dynamic properties, both conformational dynamics and diffusional properties of macromolecules. Recent simulations that address these questions are reviewed here and discussed in the context of relevant experiments.

http://pubs.acs.org/doi/pdf/10.1021/acs.jpcb.7b03570

Crowding in Cellular Environments at an Atomistic Level from Computer Simulations.

Traditionally, biochemical studies are performed in dilute homogenous solutions, which are very different from the dense mixture of molecules found in cells. Thus, the physiological relevance of these studies is in question. This recognition motivated scientists to formulate the effect of crowded solutions in general, and excluded volume in particular, on biochemical processes. Using polymers or proteins as crowders, it was shown that while crowding tends to significantly enhance the formation of complexes containing many subunits, dimerizations are only mildly affected. Computer simulations, together with experimental evidence, indicate soft interactions and diffusion as critical factors that operate in a concerted manner with excluded volume to modulate protein binding. Yet, these approaches do not truly mimic the cellular environment. In vivo studies may overcome this shortfall. The few studies conducted thus far suggest that in cells, binding and folding occur at rates close to those determined in dilute solutions. Obtaining quantitative biochemical information on reactions inside living cells is currently a main challenge of the field, as the complexity of the intracellular milieu was what motivated crowding research to begin with.

http://absimage.aps.org/image/MAR11/MWS_MAR11-2010-020038.pdf

Formation of protein-complexes in crowded environments: from in vitro to in vivo

https://www.cell.com/biophysj/pdf/S0006-3495(14)01104-7.pdf

Diffusion within the Cytoplasm: A Mesoscale Model of Interacting Macromolecules

Protein–protein interactions are important in many essential biological functions, such as transcription, translation, and signal transduction. Much progress has been made in understanding protein–protein association in dilute solution via experimentation and simulation. Cells, however, contain various macromolecules, such as DNA, RNA, proteins, among many others, and a myriad of non-specific interactions (usually weak) are present between these cellular constituents. In this review article, we describe the important developments in recent years that have furthered our understanding and even allowed prediction of the consequences of macromolecular crowding on protein–protein interactions. We outline the development of our crowding theory that can predict the change in binding free energy due to crowding quantitatively for both repulsive and attractive protein–crowder interactions. One of the most important findings from our recent work is that weak attractive interactions between crowders and proteins can actually destabilize protein complex formation as opposed to the commonly assumed stabilizing effect predicted based on traditional crowding theories that only account for the entropic-excluded volume effects. We also discuss the implications of macromolecular crowding on the population of encounter versus specific native complex.

Protein-protein interactions in a crowded environment

Data-driven process monitoring and fault analysis of reformer units in hydrogen plants: Industrial application and perspectives

https://www.cell.com/biophysj/pdf/S0006-3495(12)00776-X.pdf

Smoothing of the GB1 Hairpin Folding Landscape by Interfacial Confinement

Replica exchange molecular dynamics simulations are performed on the protein complex pKID-KIX to understand the effects of macromolecular crowding on coupled folding and binding events. A structure-based protein model at the residue level is adopted for the two proteins to include intramolecular conformational flexibility, while crowding macromolecules are represented as spherical particles. The interactions between crowders and protein residues can be either purely repulsive or a combination of short-range repulsion and intermediate-range attraction. Consistent with previous studies on rigid-body protein binding in the presence of spherical crowders, we find that the complex formation is stabilized by repulsive protein-crowder interactions and destabilized by sufficiently strong attractive protein-crowder interactions. Competition between stabilizing repulsive and destabilizing attractive interactions is quantitatively captured by a previous theoretical model developed for describing the change in the binding free energy of rigid proteins in a crowded environment. We find that protein flexibility has little effect on the thermodynamics of the pKID-KIX binding (with respect to bulk) for repulsive and weakly attractive protein-crowder interactions. For strong protein-crowder attractive interactions, the destabilizing effect due to crowding is attenuated by protein flexibility. Interestingly, the mechanism of coupled folding and binding observed in bulk remains unchanged under highly crowded conditions over a broad range of protein-crowder interaction strengths. Also, strong protein-crowder attractive interactions can significantly stabilize intermediate states involving partial contact between pKID and KIX domains.

Apratim Bhattacharya

Papers

Protein-protein interactions in a crowded environment

Data-driven process monitoring and fault analysis of reformer units in hydrogen plants: Industrial application and perspectives

Smoothing of the GB1 Hairpin Folding Landscape by Interfacial Confinement

Macromolecular crowding effects on coupled folding and binding.

Development of a knowledge based hybrid neural network (KBHNN) for studying the effect of diafiltration during ultrafiltration of whey