Hydrophobic Protein Research Articles

Comparison of host cell protein removal by depth filters with diatomaceous earth and synthetic silica filter aids using model proteins.

A number of studies have demonstrated that depth filtration can provide significant adsorptive removal of host cell proteins (HCP), but there is still considerable uncertainty regarding the underlying factors controlling HCP binding. This study compared the binding characteristics of two fine grade depth filters, the X0SP (polyacrylic fiber with a synthetic silica filter aid) and X0HC (cellulose fibers with diatomaceous earth (DE) as a filter aid), using a series of model proteins with well-defined physical characteristics. Protein binding to the X0SP filter was dominated by electrostatic interactions with greatest capacity for positively-charged proteins. In contrast, the X0HC filter showed greater binding of more hydrophobic proteins although electrostatic interactions also played a role. In addition, ovotransferrin showed unusually high binding capacity to the X0HC, likely due to interactions with metals in the DE. Scanning Electron Microscopy with Energy Dispersive Spectroscopy was used to obtain additional understanding of the binding behavior. These results provide important insights into the physical phenomena governing HCP binding to both fully synthetic and natural (cellulose + DE) depth filters.

Turnover and replication analysis by isotope labeling (TRAIL) reveals the influence of tissue context on protein and organelle lifetimes

The lifespans of proteins range from minutes to years within mammalian tissues. Protein lifespan is relevant to organismal aging, as long‐lived proteins accrue damage over time. It is unclear how protein lifetime is shaped by tissue context, where both cell turnover and proteolytic degradation contribute to protein turnover. We develop turnover and replication analysis by 15N isotope labeling (TRAIL) to quantify protein and cell lifetimes with high precision and demonstrate that cell turnover, sequence‐encoded features, and environmental factors modulate protein lifespan across tissues. Cell and protein turnover flux are comparable in proliferative tissues, while protein turnover outpaces cell turnover in slowly proliferative tissues. Physicochemical features such as hydrophobicity, charge, and disorder influence protein turnover in slowly proliferative tissues, but protein turnover is much less sequence‐selective in highly proliferative tissues. Protein lifetimes vary nonrandomly across tissues after correcting for cell turnover. Multiprotein complexes such as the ribosome have consistent lifetimes across tissues, while mitochondria, peroxisomes, and lipid droplets have variable lifetimes. TRAIL can be used to explore how environment, aging, and disease affect tissue homeostasis.

Effects of high-pressure homogenization treatment on physiochemical properties of novel plant proteins

The plum seed protein isolates (PSPI), wolfberry protein isolates (WPI) jujube seed protein isolates (JPI), and hemp seed protein isolates (HPI) were prepared and treated with high-pressure homogenization at 90 MPa. The effects of high-pressure homogenization treatment on particle size, surface hydrophobicity, solubility, subunits, rheological behavior, and microstructure of proteins were investigated in this study. As compared with native proteins, the particle size of PSPI, WPI, JPI and HPI decreased 89%, 38%, 93% and 83%, respectively, after high-pressure homogenization treatment; the solubility of PSPI, WPI, JPI and HPI increased 31%, 9%, 43% and 201%, respectively. However, the effects of treatment on surface hydrophobicity and rheological behavior depended on the type of proteins. The surface hydrophobicity of WPI increased 22%, while the surface hydrophobicity of PSPI, JPI and HPI decreased 4%, 19% and 46%, respectively. The treatment also promoted the gelation of WPI, JPI and HPI. Furthermore, the composition of proteins was not affected by high-pressure homogenization treatment.

Tuning the Microstructure of Protein Corona by Nanoparticle Hydrophobicity: A Dissipative Particle Dynamics Study

Although multiple experimental methods have been used to investigate protein corona, however, the microstructure of protein corona on nanoparticles is still unknown. By using dissipative particle dynamics (DPD) simulation, we found that hydrophobic nanoparticles adsorbed more proteins than hydrophilic ones. The distance between hydrophobic nanoparticles and proteins was closer than that between hydrophilic nanoparticles and proteins. Moreover, the distribution of different-sized proteins around nanoparticles was also systematically investigated. These findings provide detailed structural information of protein corona at microscopic level.

Composition and molecular structure analysis of hydrophilic/hydrophobic extracellular polymeric substances (EPS) with impacts on sludge dewaterability

Extracellular polymeric substances (EPS) have a significant effect on the dewaterability of waste-activated sludge (WAS); however, the role of polarity distribution (hydrophilic/hydrophobic characteristics) of EPS in sludge dewatering remains unclear. In this study, the relationship between the characteristics of EPS hydrophilic/hydrophobic fractions (composition and molecular structure) and sludge physicochemical properties of 8 different sludge samples was investigated, and a structural equation model was constructed to describe the potential mechanisms of key EPS parameters on sludge dewatering. Experimental results showed that the variation in sludge EPS polarity led to significant changes in the surface hydrophilicity/hydrophobicity and structure compactness, which affected the sludge dewaterability. Specifically, the increase in the content of tyrosine-like proteins, especially those related to hydrophobic acid fraction (HPO-A), played a key role in increasing the surface hydrophobicity of sludge and promoting its dewaterability. In contrast, humic acids in hydrophilic EPS (HPI) could interact with hydrophobic proteins to form dense biopolymers (characterized by high nonprotonated nitrogen (Nnonpr) content), resulting in a more stable and compact structure of the EPS matrix (characterized by low random coil content) and deterioration of sludge dewaterability. This study provides a new perspective for the exploration of the relationship between hydrophilic/hydrophobic biopolymers and sludge dewaterability.

Interaction of the periplasmic chaperone SurA with the inner membrane protein secretion (SEC) machinery.

Gram-negative bacteria are surrounded by two protein-rich membranes with a peptidoglycan layer sandwiched between them. Together they form the envelope (or cell wall), crucial for energy production, lipid biosynthesis, structural integrity, and for protection against physical and chemical environmental challenges. To achieve envelope biogenesis, periplasmic and outer-membrane proteins (OMPs) must be transported from the cytosol and through the inner-membrane, via the ubiquitous SecYEG protein-channel. Emergent proteins either fold in the periplasm or cross the peptidoglycan (PG) layer towards the outer-membrane for insertion through the β-barrel assembly machinery (BAM). Trafficking of hydrophobic proteins through the periplasm is particularly treacherous given the high protein density and the absence of energy (ATP or chemiosmotic potential). Numerous molecular chaperones assist in the prevention and recovery from aggregation, and of these SurA is known to interact with BAM, facilitating delivery to the outer-membrane. However, it is unclear how proteins emerging from the Sec-machinery are received and protected from aggregation and proteolysis prior to an interaction with SurA. Through biochemical analysis and electron microscopy we demonstrate the binding capabilities of the unoccupied and substrate-engaged SurA to the inner-membrane translocation machinery complex of SecYEG-SecDF-YidC - aka the holo-translocon (HTL). Supported by AlphaFold predictions, we suggest a role for periplasmic domains of SecDF in chaperone recruitment to the protein translocation exit site in SecYEG. We propose that this immediate interaction with the enlisted chaperone helps to prevent aggregation and degradation of nascent envelope proteins, facilitating their safe passage to the periplasm and outer-membrane.

Post-translational palmitoylation of metabolic proteins.

Numerous cellular proteins are post-translationally modified by addition of a lipid group to their structure, which dynamically influences the proteome by increasing hydrophobicity of proteins often impacting protein conformation, localization, stability, and binding affinity. These lipid modifications include myristoylation and palmitoylation. Palmitoylation involves a 16-carbon saturated fatty acyl chain being covalently linked to a cysteine thiol through a thioester bond. Palmitoylation is unique within this group of modifications, as the addition of the palmitoyl group is reversible and enzyme driven, rapidly affecting protein targeting, stability and subcellular trafficking. The palmitoylation reaction is catalyzed by a large family of Asp-His-His-Cys (DHHCs) motif-containing palmitoyl acyltransferases, while the reverse reaction is catalyzed by acyl-protein thioesterases (APTs), that remove the acyl chain. Palmitoyl-CoA serves an important dual purpose as it is not only a key metabolite fueling energy metabolism, but is also a substrate for this PTM. In this review, we discuss protein palmitoylation in regulating substrate metabolism, focusing on membrane transport proteins and kinases that participate in substrate uptake into the cell. We then explore the palmitoylation of mitochondrial proteins and the palmitoylation regulatory enzymes, a less explored field for potential lipid metabolic regulation.

Physicochemical stability, antioxidant activity, and antimicrobial activity of quercetin-loaded zein nanoparticles coated with dextrin-modified anionic polysaccharides

Core-shell biopolymer nanoparticles are assembled from a hydrophobic protein (zein) core and a hydrophilic polysaccharide (carboxymethyl dextrin) shell. The nanoparticles were shown to have good stability and the ability to protect quercetin from chemical degradation under long-term storage, pasteurization, and UV irradiation. Spectroscopy analysis shows that electrostatic, hydrogen bonding, and hydrophobic interactions are the main driving forces for the formation of composite nanoparticles. Quercetin coated with nanoparticles significantly enhanced its antioxidant and antibacterial activities and showed good stability and slow release in vitro during simulated gastrointestinal digestion. Furthermore, the encapsulation efficiency of carboxymethyl dextrin-coated zein nanoparticles (81.2%) for quercetin was significantly improved compared with that of zein nanoparticles alone (58.4%). These results indicate that carboxymethyl dextrin-coated zein nanoparticles can significantly improve the bioavailability of hydrophobic nutrient molecules such as quercetin and provide a valuable reference for their application in the field of biological delivery of energy drinks and food.

Effect of anthocyanins on mechanical and physicochemical properties of wheat dough

The effects of anthocyanins (ACNs) on the mechanical properties of dough (including farinographic properties, tensile properties and textural properties) and the physicochemical interaction between ACNs and wheat gluten protein polymer were studied by using conventional addition of ACNs. The mechanical test results show that the dough containing ACNs has higher strength, better stability and stronger elasticity than the dough without ACNs, and can maintain the elasticity after long-term mechanical mixing. The surface hydrophobicity of wheat gluten protein decreased and the hydrogen bond increased, indicating that the addition of ACNs stabilized the spatial structure of protein. In addition, the disulfide bonds in ACNs-added samples were increased, suggesting that the current dosage of ACNs improved the network structure of gluten proteins. The basic physicochemical properties and texture characteristics of ACNs-rich dough were discussed in this study, which can provide data reference for the production and application of related dough products.

Mechanical Properties of Protein-Based Hydrogels Derived from Binary Protein Mixtures-A Feasibility Study.

Hydrogels based on natural polymers such as proteins are considered biocompatible and, therefore, represent an interesting class of materials for application in the field of biomedicine and high-performance materials. However, there is a lack of understanding of the proteins which are able to form hydrogel networks by photoinduced dityrosine crosslinking as well as a profound knowledge of the formed network itself and the mechanisms which are responsible for the resulting mechanical properties of such protein-based hydrogels. In this study, casein, bovine serum albumin, α-amylase, and a hydrophobic elastin-like protein were used to prepare binary protein mixtures with defined concentration ratios. After polymerization, the mechanical properties of the resulting homopolymeric and copolymeric hydrogels were determined using rheological methods depending on the protein shares used. In additional uniaxial compression tests, the fracture strain was shown to be independent of the protein shares, while hydrogel toughness and compressive strength were increased for protein-based hydrogels containing casein.

Canonical Wnt signaling activation by chimeric antigen receptors for efficient cardiac differentiation from mouse embryonic stem cells

BackgroundCanonical Wnt signaling is involved in a variety of biological processes including stem cell renewal and differentiation, embryonic development, and tissue regeneration. Previous studies reported the stage-specific roles of the Wnt signaling in heart development. Canonical Wnt signal activation by recombinant Wnt3a in the early phase of differentiation enhances the efficiency of myocardial cell production from pluripotent stem cells. However, the hydrophobicity of Wnt proteins results in high cost to produce the recombinant proteins and presents an obstacle to their preparation and application for therapeutics, cell therapy, or molecular analysis of Wnt signaling.MethodsTo solve this problem, we generated an inexpensive molecule-responsive differentiation-inducing chimeric antigen receptor (designated as diCAR) that can activate Wnt3a signaling. The extracellular domains of low-density-lipoprotein receptor-related protein 6 (LRP6) and frizzeled-8 (FZD8) were replaced with single-chain Fv of anti-fluorescein (FL) antibody, which can respond to FL-conjugated bovine serum albumin (BSA-FL) as a cognate ligand. We then analyzed the effect of this diCAR on Wnt signal activation and cardiomyocyte differentiation of mouse embryonic stem cells in response to BSA-FL treatment.ResultsEmbryonic stem cell lines stably expressing this paired diCAR, named Wnt3a-diCAR, showed TCF/β-catenin-dependent transactivation by BSA-FL in a dose-dependent manner. Treatment with either Wnt3a recombinant protein or BSA-FL in the early phase of differentiation revealed similar changes of global gene expressions and resulted in efficient myocardial cell differentiation. Furthermore, BSA-FL-mediated signal activation was not affected by a Wnt3a antagonist, Dkk1, suggesting that the signal transduction via Wnt3a-diCAR is independent of endogenous LRP6 or FZD8.ConclusionWe anticipate that Wnt3a-diCAR enables target-specific signal activation, and could be an economical and powerful tool for stem cell-based regeneration therapy.

Bio-Based Nano-Enabled Cosmetic Formulations for the Treatment of Cutibacterium acnes-Associated Skin Infections.

Acne is a common chronic skin condition with serious physical and psychosocial consequences. In some cases, the appearance of pimples, whiteheads, or blackheads on the face, neck, and back may lead to scarring, disfiguring, depression, frustration, and anxiety in patients. Current treatments rely on antibiotics to eradicate Cutibacterium acnes (C. acnes), the bacterium responsible for this skin condition. However, these approaches do not scavenge the reactive oxidative species (ROS) generated during disease development and raise concerns about the increase in antimicrobial resistance. In this study, an environmentally friendly and cost-effective self-assembly nanoencapsulation technology based on zein, a bio-based hydrophobic protein, was employed to produce multifunctional essential oil (EO)-loaded nanocapsules (NCs) with superior antioxidant and bactericidal activity toward C. acnes. The NCs displayed "smart" release of the active cargo only under the conditions that were conducive to acne proliferation on skin. Once incorporated into creams, the EO-loaded NCs led to a complete inhibition of C. acnes and demonstrated the capacity to scavenge ROS, thus preventing damage to human skin cells. The in vitro permeation studies revealed that the nanoformulated EO was able to penetrate through the epidermis, indicating its potential for the treatment of skin diseases, such as acne.

Chirality of tyrosine controls biofilm formation via the regulation of bacterial adhesion

Biofilm is the main cause of membrane biofouling and microbial corrosion. One of the most efficient strategies for biofilm reduction is inhibiting bacteria adhesion. In this study, we selected D-tyrosine to inhibit the adhesion of Escherichia coli, and the molecular response and metabolic pathways of E. coli were explored with transcriptome analysis. D-tyrosine could obviously inhibit the bacterial adhesion via lowering the adhesion force. The number of extracellular proteins decreased by 45% in the presence of D-tyrosine, leading to less hydrophobicity and autonomous aggregation of cells. Furthermore, transcriptome analysis showed that the inhibitory ability of D-tyrosine to the adhesion of E. coli decreased with time. At the initial stage, D-tyrosine could regulate tryptophan, curli, peptidoglycan, and adhesion-like protein synthesis, leading to less extracellular protein and lower cell hydrophobicity, and thus reduce cell aggregation and surface adhesion. This study provides a better understanding for the roles of D-amino acids in bacterial adhesion and develops a new strategy for biofilm reduction to mitigate membrane biofouling and microbial corrosion.

Interactive effects of dual short-chain n-alkanes on removal performances and microbial responses of biotrickling filters

Enhanced biotrickling filtration at the presence of surfactants could be competitive in treatment of waste gas streams polluted by hydrophobic volatile organic compounds (VOCs) such as light hydrocarbons, while few such reports are available. Herein, biotrickling filters (BTFs) were applied to investigate the removal performances for binary-component n-alkanes (n ≤ 6) at the presence of sodium dodecyl benzene sulfonate (SDBS), and the microbial responses were also examined. Interestingly, results showed that the existence of shorter chain n-alkanes promoted the removal of longer chain n-alkanes, as the elimination capacities (EC) of BTF for n-hexane increased by 44 ± 1.2 % when there was methane in incoming gas stream. While the presence of longer chain n-alkanes antagonistically affected shorter chain n-alkane removal, as EC for methane decreased by 65 ± 8.1 % at the presence of n-hexane. Additionally, the presence of SDBS improved the mixed n-alkane removal. EC of the BTF with 15 mg/L SDBS for mixed propane and n-hexane reached 55 ± 1.4 and 31 ± 0.5 g/m3·h respectively, which increased by 90 ± 4.6 % and 47 ± 0.9 % compared with those without SDBS. The richness of Bacillus and Sporosarcina was improved in the BTF fed with SDBS. Moreover, the presence of SDBS improved the content of hydrophobic proteins and the activity of fluorescent substances inextracellular polymeric substances. Also, both the activities of ATPase and the antioxidant capacity of microbial cells exhibited higher than that when SDBS was not added. These data could lead to a better understanding and more reasonable design of biotrickling filtration to remove n-alkanes from waste gas streams of refinery wastewater treatment plants.

Effect of air frying and baking on physicochemical properties and digestive properties of scallop (Patinopecten yessoensis) adductor muscle

In this study, the effects of dry heat treatments including air frying and baking on the physicochemical and digestive properties of proteins in scallop adductor muscle (SAM) were evaluated. After heat treatments, the proteins in SAM exhibited different degrees of oxidation, aggregation and degradation. For both heat treatments, the increase of carbonyl and dityrosine contents and the decrease of free sulfhydryl groups and surface hydrophobicity of proteins in SAM were observed along with increasing heat temperature. Meanwhile, with increasing heat temperature, there was a progressive transition from α-helix to β-sheet in protein secondary structure. However, the protein solubility first increased and then decreased with increasing temperature. Among which, the solubility of 160°C-treated samples was the highest, which were 21.02% and 20.32% for air frying and baking. The protein digestive properties which reflected by the degree of hydrolysis (DH), soluble amino groups and soluble peptides showed a trend of increasing first and then decreasing with increasing temperature. After gastrointestinal digestion, the DH, soluble amino groups and soluble peptides of 160°C-treated SAMs cooking by air frying were 69.96%, 61.14% and 39.33%, respectively, which were significantly higher than all other samples including the fresh ones. Correlation analysis showed that the protein digestive indexes were positively correlated with solubility, free sulfhydryl content and surface hydrophobicity, and negatively correlated with protein carbonyl content, dityrosine content and protein aggregation degree. These results provide evidence for knowing more about the effects of dry heat treatments on physicochemical and digestive properties of aquatic muscle food.

Pulmonary surfactant structure as solved by neutron reflectometry and atomic force microscopy.

In order to sustain breathing mechanics, the alveolar surface needs to be covered by pulmonary surfactant, a lipid/protein system that provides with the required surface tension reduction to avoid alveolar collapse at the end of expiration. Any disruption of this system could impair its function leading to severe respiratory pathologies. Pulmonary surfactant is composed by 90 % lipids and 10 % hydrophilic (SP-A and SP-D) and hydrophobic (SP-B and SP-C) proteins. After secretion, surfactant lipids form a complex structure at the alveolar air-liquid interface consisting of an adsorbed monolayer connected to a membranous reservoir in the subphase maintained thanks to the action of both hydrophobic proteins. The molecular mechanism of surfactant proteins is still not fully understood, making the finding of treatments for some respiratory pathologies a challenge. Model lipid systems mimicking pulmonary surfactant composition (DPPC/POPC/POPG 50:25:15 w:w:w) in the presence of SP-B and/or SP-C, as well as a native surfactant isolated from animal lungs, have been used as models for the study of the structure and function of pulmonary surfactant films. In this work, we have characterized these models with different biophysical technics such as neutron reflectometry and atomic force microscopy. The results point to the importance of hydrophobic proteins in the formation of three-dimensional structures associated to highly compressed surfactant films. Furthermore, a recently isolated human amniotic fluid surfactant has also been studied. This material is thought to maintain the properties of a freshly synthetized and secreted surfactant that could cover the air-liquid interface in a more efficient way, with physiological importance to develop new surfactant therapies. Here we show that amniotic fluid surfactant exhibits a similar behavior than animal-derived surfactant once it coats the interface.

Structural, functional, and physicochemical characterization of fermented whey protein concentrates recovered from various fermented-distilled whey

The utilization of whey has become a challenge with the significant growth in the production of cheese and coagulated milk products. Consequently, we have developed cost-effective and waste-free production technologies for processing whey disposal into a variety of high-quality, value-added food products at the industrial level. This work constitutes a research on the impact of various alcoholic fermentations on functional, structural, and physicochemical properties of fermented whey proteins recovered from whey-based spirit production effluent. The results showed that surface hydrophobicity and sulfhydryl groups of fermented whey protein concentrates (FWPC) increased significantly in comparison with native whey protein concentrate, while the zeta-potential and particle size of non-supplemented FWPC and low-supplemented FWPC were not substantially affected by fermentation. Furthermore, the outcomes indicated that the non-and low-supplemented whey fermentation led to the improvement in the solubility of FWPCs dispersions, and enhancement in the emulsifying activity and stability of FWPCs. Size exclusion chromatography and SDS-Page results also demonstrated significantly increased β-Lg content in FWPCs, which might be attributed to the reinforcement of the β-Lg intramolecular and noncovalent bonds. The enhancement in functionality was probably due to the partially unfolded whey protein molecules, exposing more hydrophobic amino acid residues, thus making the protein more amphiphilic and capable. Nevertheless, high-yield alcoholic fermentation led to critical changes in the structural properties of whey proteins as evidenced by SEM results. Therefore, our findings suggested that the application of recovering FWPCs after producing premium quality potable whey-based spirit from the presence of non-and low-lactose supplemented whey is fully proposed as an industrially recommended alternative for food-grade protein production. • Fermentation process significantly increased general properties of FWPC. • More amphiphilic and capable proteins recovered due to exposed hydrophobic amino acids. • Increased β-Lg content in fermented whey protein leads to better functionality. • FWPC is proposed for manufacturing food-grade protein at the industrial level.

A vibrational spectroscopic approach to elucidate the molecular mechanism behind the channel activity of viroporins.

The prevalence of diseases caused by pathogenic viruses and the scarcity of treatment and vaccination options call for extensive research of the molecular mechanisms underlying the function of these viruses. Small hydrophobic viral proteins with ion channel activity, so-called viroporins, are involved in the virus particle entry into and release from the host cell. One of these viroporins, the Influenza A M2 channel, has shown to be the target for anti-viral drugs motivating spectroscopic investigations of other viroporins to understand their relevance as potential anti-viral treatment targets. We used the Influenza A M2 viroporin as a model system to establish a vibrational spectroscopic approach to examine the gating mechanism and proton conductance of this pH-activated proton channel. In this work, we immobilized reconstituted M2 on a self-assembled monolayer bound to a nanostructured gold film that can be used for surface-enhanced infrared absorption (SEIRA) spectroscopy. Employing pH-induced SEIRA difference spectroscopy we monitor protonation events and changes in the α-helix amide I absorption due to a pH-dependent channel opening that leads to proton conductivity. Furthermore, the surface selection rule of SEIRA enabled us to observe the reorientation of the α-helical structures associated with the channel opening in-situ. Combining the spectroscopic data with computational vibrational spectroscopic calculations we model the large-scale reorganization of M2's α-helices, and by this quantify the opening angle of the channel transitioning from closed to the activated state. We aim to utilize this approach to enable a combined structural and functional analysis of viroporins of current relevance.

Curcumin-encapsulated hydrophilic gelatin nanoparticle to stabilize fish oil-loaded Pickering emulsion

Herein, pH-cycle method was explored to prepare curcumin-encapsulated hydrophilic bovine bone gelatin (BBG/Cur) nanoparticle and then the obtained nanoparticle was applied to stabilize fish oil-loaded Pickering emulsion. The nanoparticle had a high encapsulation efficiency (93.9 ± 0.5 %) and loading capacity (9.4 ± 0.1 %) for curcumin. The nanoparticle-stabilized emulsion had higher emulsifying activity index (25.1 ± 0.9 m2/g) and lower emulsifying stability index (161.5 ± 18.8 min) than BBG-stabilized emulsion. The pH affected the initial droplet sizes and creaming index values of the Pickering emulsions: pH 11.0 < pH 5.0 ≈ pH 7.0 ≈ pH 9.0 < pH 3.0. Curcumin provided obvious antioxidant effect for the emulsions, which was also dependent on pH. The work suggested pH-cycle method could be used to prepare hydrophobic antioxidant-encapsulated hydrophilic protein nanoparticle. It also provided basic information on the development of protein nanoparticles for Pickering emulsion stabilization.

Characterizing the hydrophobicity of proteins to predict protein assembly.

The hydrophobic effect is a crucial driver for many biomolecular interactions, including protein folding, protein-protein association, protein-ligand binding, and micelle formation. Among these, protein-protein interactions are significant for most physiological and pathological processes, such as immune response, signal transduction, and enzyme catalysis. The protein-protein interaction interfaces involve hydrophobic patches, which are not only influenced by the chemistry of the underlying amino acid residues but also depend on the surface patterns. The previously reported approaches either fail to capture the chemical and geometrical patterns of the heterogeneous surface or are computationally expensive. We have developed a new computational method that provides the collective response of water to the topological features of the proteins. We investigated an array of globular and intrinsically disordered proteins and identified hydrophobic patches of proteins that lead to protein assembly. The results are in excellent agreement with those published in the literature. Our results show that amino acids exhibit disparate hydration properties depending on the local topography of the protein. In addition, this method enables us to quantitatively compare the hydrophobicity of different proteins relative to each other.