Biosystems最新文献

{"title":"Deciphering the dynamic binding of spicy odorants to human olfactory receptors","authors":"Jingtao Wang ,&nbsp;Chenglei Zhang ,&nbsp;Juncang Peng ,&nbsp;Jian Wu ,&nbsp;Shan Wang ,&nbsp;Wu Fan ,&nbsp;Qingzhao Shi ,&nbsp;Qidong Zhang ,&nbsp;Guobi Chai","doi":"10.1016/j.biosystems.2026.105703","DOIUrl":"10.1016/j.biosystems.2026.105703","url":null,"abstract":"<div><div>In this study, we compiled three categories of odorants with spicy aromas: anise class, clove class, and cinnamon class. We aimed to use molecular dynamics simulation techniques to uncover potential regularities in the activation mechanisms of the same odorant across different olfactory receptors, or vice versa, the activation mechanisms of different odorants on the same olfactory receptor. Here, molecular dynamics simulation results reveal that anisaldehyde and estragole preferentially bind to TYR residues, thereby activating the corresponding olfactory receptors. Both eugenol and isoeugenol activate OR5D18 at similar binding sites, but ultimately lead to differential conformational changes in the olfactory receptor. Additionally, the binding conformations of eugenol and methyl eugenol are nearly identical, whereas cinnamaldehyde and cinnamyl alcohol, methyl cinnamaldehyde, exhibit distinct binding conformations with the olfactory receptor. These results underscore how subtle structural changes can impact the binding mechanism of odorants.</div></div>","PeriodicalId":50730,"journal":{"name":"Biosystems","volume":"260 ","pages":"Article 105703"},"PeriodicalIF":1.9,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145946488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Darwin to teleonomy: A categorical final-cause calculus for evolution","authors":"Andrei T. Patrascu","doi":"10.1016/j.biosystems.2025.105687","DOIUrl":"10.1016/j.biosystems.2025.105687","url":null,"abstract":"&lt;div&gt;&lt;div&gt;We propose a &lt;em&gt;teleonomical calculus&lt;/em&gt; for evolution that generalizes the classical Darwin–Fisher picture by making &lt;em&gt;final causes&lt;/em&gt; – what systems keep true about themselves – into mathematical objects with universal properties. In our framework, the state space is a category &lt;span&gt;&lt;math&gt;&lt;mi&gt;C&lt;/mi&gt;&lt;/math&gt;&lt;/span&gt; acted upon (laxly) by time &lt;span&gt;&lt;math&gt;&lt;mi&gt;T&lt;/mi&gt;&lt;/math&gt;&lt;/span&gt;, and viability constraints live in a fibration &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mi&gt;p&lt;/mi&gt;&lt;mo&gt;:&lt;/mo&gt;&lt;mi&gt;E&lt;/mi&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mo&gt;→&lt;/mo&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mi&gt;C&lt;/mi&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;. An &lt;em&gt;endogenous&lt;/em&gt; functor &lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mi&gt;G&lt;/mi&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mi&gt;t&lt;/mi&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;mo&gt;:&lt;/mo&gt;&lt;mi&gt;C&lt;/mi&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mo&gt;→&lt;/mo&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mi&gt;E&lt;/mi&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt; extracts invariants from the system (e.g. topological features via persistent homology, sheaf gluing compatibilities, symmetry/conservation laws, or behavioral attractors). The present compatible with realizing these constraints at horizon &lt;span&gt;&lt;math&gt;&lt;mi&gt;t&lt;/mi&gt;&lt;/math&gt;&lt;/span&gt; is the right Kan extension &lt;span&gt;&lt;span&gt;&lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mi&gt;Tel&lt;/mi&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mi&gt;t&lt;/mi&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;mrow&gt;&lt;mo&gt;(&lt;/mo&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mi&gt;X&lt;/mi&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mn&gt;0&lt;/mn&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;mo&gt;)&lt;/mo&gt;&lt;/mrow&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mo&gt;=&lt;/mo&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mo&gt;Ran&lt;/mo&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mi&gt;ι&lt;/mi&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;mi&gt;Φ&lt;/mi&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mrow&gt;&lt;mo&gt;(&lt;/mo&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mi&gt;X&lt;/mi&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mn&gt;0&lt;/mn&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;mo&gt;)&lt;/mo&gt;&lt;/mrow&gt;&lt;mo&gt;,&lt;/mo&gt;&lt;/mrow&gt;&lt;/math&gt;&lt;/span&gt;&lt;/span&gt;&lt;/span&gt;equivalently a (possibly enriched) limit or a largest invariant subcoalgebra. Passing to concrete dynamics &lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mi&gt;x&lt;/mi&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mi&gt;t&lt;/mi&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt; yields an &lt;em&gt;endogenous bias&lt;/em&gt; that selects among feasible futures without introducing exogenous rewards: &lt;span&gt;&lt;span&gt;&lt;span&gt;&lt;math&gt;&lt;mrow&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mi&gt;d&lt;/mi&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mi&gt;x&lt;/mi&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mi&gt;t&lt;/mi&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;mo&gt;=&lt;/mo&gt;&lt;mi&gt;f&lt;/mi&gt;&lt;mrow&gt;&lt;mo&gt;(&lt;/mo&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mi&gt;x&lt;/mi&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mi&gt;t&lt;/mi&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;mo&gt;,&lt;/mo&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mi&gt;e&lt;/mi&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mi&gt;t&lt;/mi&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;mo&gt;)&lt;/mo&gt;&lt;/mrow&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mi&gt;d&lt;/mi&gt;&lt;mi&gt;t&lt;/mi&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mo&gt;−&lt;/mo&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mi&gt;ɛ&lt;/mi&gt;&lt;msub&gt;&lt;mrow&gt;&lt;","PeriodicalId":50730,"journal":{"name":"Biosystems","volume":"260 ","pages":"Article 105687"},"PeriodicalIF":1.9,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding life: A detailed examination of program collection","authors":"Jun Cao","doi":"10.1016/j.biosystems.2026.105693","DOIUrl":"10.1016/j.biosystems.2026.105693","url":null,"abstract":"<div><div>This article introduces the theory that “life is a collection of programs”. According to this theory, life constitutes a complex system composed of genetic information, metabolic regulation, developmental differentiation, and neurocognitive programs. These components operate in an orderly manner through initiation, execution, feedback, and repair mechanisms. Philosophically, ancient Greek atomism, the Yin-Yang Five Elements theory, and Hegelian dialectics provide support for the structural and dynamic properties of this theory. Scientifically, cell theory, genetics, and synthetic biology have validated its material basis. Specifically, genetic programs regulate traits through DNA, metabolic programs maintain homeostasis through enzymes and signaling pathways, developmental programs rely on gene networks to shape biological structures, and neural programs achieve cognition through neuronal signals. While this theory breaks through the traditional perspectives on life, it also faces challenges such as the “hard problem of consciousness” and ethical controversies. Looking ahead, integrating single-cell omics and artificial intelligence modeling is essential to deepen research and construct a robust ethical framework. This theory provides an interdisciplinary paradigm for life sciences and promotes the advancement of medicine and biotechnology.</div></div>","PeriodicalId":50730,"journal":{"name":"Biosystems","volume":"260 ","pages":"Article 105693"},"PeriodicalIF":1.9,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expert-guided multi-objective optimization: An efficient strategy for parameter estimation of biological systems with limited data","authors":"Léa Da Costa Fernandes ,&nbsp;David Bernard ,&nbsp;François Pérès ,&nbsp;Paul Monsarrat ,&nbsp;Béatrice Cousin ,&nbsp;Sylvain Cussat-Blanc","doi":"10.1016/j.biosystems.2025.105686","DOIUrl":"10.1016/j.biosystems.2025.105686","url":null,"abstract":"<div><div>Calibrating biological models is challenging due to high-dimensional parameter spaces and the limited availability of reliable experimental data. In this study, we propose a hybrid calibration framework that integrates expert knowledge into a multi-objective optimization process. We have evaluated three multi-objective optimization algorithm (NSGA-III, MOEA/D and MO-TPE) with our framework to combine hard constraints derived from biological measurements with soft constraints encoding qualitative domain expertise, such as expected curve shapes or event timing. This dual-constraint strategy guides the search toward biologically plausible parameter sets while preserving flexibility and interpretability. We demonstrate the effectiveness of our method on a benchmark model of skin wound healing, comparing it to standard and unconstrained optimization strategies. Results show that the framework reduces the risk of overfitting to sparse time-course data by favoring dynamically plausible trajectories that satisfy expert-guided soft constraints, increasing the proportion of biologically plausible solutions generated from 1.8% <span><math><mo>±</mo></math></span> 1.3 to 24.3% <span><math><mo>±</mo></math></span> 8.6 for NSGA-III without constraint to NSGA-III with 6 constraints, respectively (<span><math><mrow><mi>p</mi><mo>&lt;</mo><mn>0</mn><mo>.</mo><mn>0001</mn></mrow></math></span>). The framework is flexible, iterative, and generalizable, offering a principled way to leverage domain knowledge for model calibration in complex biological systems.</div></div>","PeriodicalId":50730,"journal":{"name":"Biosystems","volume":"260 ","pages":"Article 105686"},"PeriodicalIF":1.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145901519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects along the epithelial-mesenchymal biointerface in direct cell self-organisation: Multiscale theoretical analysis","authors":"Ivana Pajic-Lijakovic ,&nbsp;Milan Milivojevic ,&nbsp;Peter V.E. McClintock","doi":"10.1016/j.biosystems.2025.105690","DOIUrl":"10.1016/j.biosystems.2025.105690","url":null,"abstract":"<div><div>Epithelial cancer ranks among the most deadly types of cancer globally. Focusing on the disease's early stages could lead to significant enhancements in the survival rates of cancer patients. The initial phase of the disease is associated with the dissemination of cancer cells into the adjacent healthy epithelium. Therefore, a more profound understanding of cell dynamics at the biointerface between epithelial and cancer (mesenchymal) cells is essential for managing the disease promptly. The dynamics of cells at this epithelial-cancer biointerface arises through interplay between a variety of biological and physical mechanisms. Although considerable research has been dedicated to examining the spread of cancer cells across the epithelium, the physical mechanisms that govern the dynamics at the biointerface remain poorly understood. The main goal of this multi-scale theoretical consideration is to emphasize the influence of physical factors, such as the viscoelasticity of the subpopulations and the dilational viscoelasticity of the biointerface, on the efficiency with which cancer spreads through the epithelium. We do so by consideration of the mechanical coupling between the epithelial and cancer mesenchymal-like subpopulations. In this review, we consider this complex phenomenon from a multiscale mechanical perspective that has not been explicitly addressed in earlier studies, using model systems such as the segregation of co-cultured epithelial–mesenchymal spheroids. The mechanical-coupling between the subpopulations arising from the system's viscoelasticity is discussed from the cellular to supracellular levels in order to recognize the main physical factors responsible for the spreading of cancer.</div></div>","PeriodicalId":50730,"journal":{"name":"Biosystems","volume":"259 ","pages":"Article 105690"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overview of the fifth special issue in Code Biology","authors":"Marcello Barbieri","doi":"10.1016/j.biosystems.2025.105643","DOIUrl":"10.1016/j.biosystems.2025.105643","url":null,"abstract":"","PeriodicalId":50730,"journal":{"name":"Biosystems","volume":"259 ","pages":"Article 105643"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145460132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anthropogenesis and the origin of human consciousness","authors":"Pedro C. Marijuán,&nbsp;Abir U. Igamberdiev,&nbsp;Terrence W. Deacon,&nbsp;Giuseppe Iurato","doi":"10.1016/j.biosystems.2025.105668","DOIUrl":"10.1016/j.biosystems.2025.105668","url":null,"abstract":"<div><div>The special issue of BioSystems, “Anthropogenesis and the origin of human consciousness”, provides an overview of the state of the art in the fields of anthropogenesis, evolution of consciousness, and social dynamics. The contributions in this special issue present the contemporary approaches to the origins of modern man and early human evolution, the development of human consciousness and its physical basis, the origin of language and art, the formation of early civilizations, the development of information systems, and even forecasting the future progress of global civilization.</div></div>","PeriodicalId":50730,"journal":{"name":"Biosystems","volume":"259 ","pages":"Article 105668"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145726626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transformation of the inherent energy in food to ATP and transformations of our knowledge about the mechanism","authors":"Ole H. Petersen CBE FRS","doi":"10.1016/j.biosystems.2025.105681","DOIUrl":"10.1016/j.biosystems.2025.105681","url":null,"abstract":"","PeriodicalId":50730,"journal":{"name":"Biosystems","volume":"259 ","pages":"Article 105681"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145745530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward a unified theory of ATP synthesis/hydrolysis: Integrating physics, chemistry, and biology","authors":"Victor Wray,&nbsp;Carey Witkov,&nbsp;Bjarne Andresen","doi":"10.1016/j.biosystems.2025.105680","DOIUrl":"10.1016/j.biosystems.2025.105680","url":null,"abstract":"","PeriodicalId":50730,"journal":{"name":"Biosystems","volume":"259 ","pages":"Article 105680"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145764535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A hybrid DNN model using novel integrated interface features for predicting protein-protein complexes binding affinity","authors":"Lichao Zhang ,&nbsp;Zhengyan Bian ,&nbsp;Xue Wang ,&nbsp;Liang Kong","doi":"10.1016/j.biosystems.2025.105688","DOIUrl":"10.1016/j.biosystems.2025.105688","url":null,"abstract":"<div><div>Accurately predicting binding affinity of protein-protein complexes is significant for gaining deeper insights into complex biological mechanisms. Given that binding between proteins primarily occurs at the interface region, previous studies have demonstrated that the number of inter-residue contacts (ICs) and the buried surface area (BSA) are critical interface features. However, existing models generally used these two types of interface features separately, ignoring integrating them effectively to achieve high prediction accuracy. In this study, utilizing kernel density estimation-based mutual information and the Hadamard product, we proposed an effective approach that integrates BSA and ICs to construct the novel integrated interface features that embody dual structural information, and further derived our feature set. Subsequently, the proposed feature set was input Deep Neural Network (DNN), and a hybrid DNN model was further developed following our hybrid modeling strategy. To enhance its prediction performance, a combined activation function was customized for the output layers. Ultimately, using four-fold cross-validation, our hybrid DNN model achieved a Pearson correlation coefficient (R) of 0.88 and a root mean square error (RMSE) of 1.301 kcal/mol, and we verified its good generalization capability, achieving R = 0.82 and RMSE = 1.21 kcal/mol on the external test set derived from the SKEMPI 2.0 database. Compared with existing approaches, our method consistently exhibited superior predictive performance, validating the effectiveness of the proposed method for protein-protein binding affinity prediction. Moreover, the integration strategy for binding affinity representation and the hybrid modeling method may be helpful for related research.</div></div>","PeriodicalId":50730,"journal":{"name":"Biosystems","volume":"260 ","pages":"Article 105688"},"PeriodicalIF":1.9,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145890426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}