@article{Maureira2026,

title = {A KCNC1 variant linked to Rett syndrome disrupts ER to Golgi trafficking of Kv3.1 channel},

author = {Diego Maureira and Carla Rubilar and Joaquín López and Paola Santander and Hans Moldenhauer and Ian Silva and Pablo Cruz and Denise Riquelme and Javiera Baeza and Wendy González and Patricio Orio and Evrim Servili and Mónica Troncoso and Elías Leiva-Salcedo and Oscar Cerda},

doi = { 10.1073/pnas.2424514123},

year  = {2026},

date = {2026-03-12},

abstract = {Intrinsic neuronal excitability, defined by the balance between input and output signals, is crucial to neural function, and its disruption underlies various neurological diseases. Kv3.1 channels, encoded by KCNC1, are essential for high-frequency action potential firing. Variants in these channels are associated with several subtypes of epilepsy. We report a patient with developmental regression and epilepsy, meeting Rett syndrome criteria, who carries a KCNC1 variant encoding the S474C substitution in Kv3.1 (Kv3.1S474C). Electrophysiological and biochemical assays reveal that Kv3.1S474C reduces channel presence in the plasma membrane and is retained in the endoplasmic reticulum. In murine primary cortical neuron cultures expressing Kv3.1S474C, we observed reduced neuronal firing frequency and exclusion of the channel from the axon initial segment. Consistently, we found a decreased firing frequency using a conductance-based computational neuronal model. In summary, this study identifies a link between a KCNC1 variant and Rett syndrome, highlighting the importance of S474 residue in Kv3.1 channel trafficking and function in neurons.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bedoya2024,

title = {Moltiverse: Molecular Conformer Generation Using Enhanced Sampling Methods},

author = {Mauricio Bedoya and Francisco Adasme-Carreño and Paula Andrea Peña-Martínez and Camila Muñoz-Gutiérrez and Luciano Peña-Tejo and José C. E. Márquez Montesinos and Erix W. Hernández-Rodríguez and Wendy González and Leandro Martínez and Jans Alzate-Morales},

url = {https://chemrxiv.org/engage/chemrxiv/article-details/67621d996dde43c908780be8},

doi = {10.26434/chemrxiv-2024-qs0pc-v2},

year  = {2025},

date = {2025-05-27},

urldate = {2024-12-01},

publisher = {Chemistry},

abstract = {Accurately predicting the diverse bound-state conformations of small molecules is crucial for successful drug discovery and design, particularly when detailed protein-ligand interactions are unknown. Established tools exist, but efficiently exploring the vast conformational space remains challenging. This work introduces Moltiverse, a novel protocol using enhanced sampling molecular dynamics (MD) simulations for conformer generation. The extended adaptive biasing force (eABF) algorithm combined with metadynamics, guided by a single collective variable (radius of gyration, RDGYR), efficiently samples the conformational landscape of a small molecule. Moltiverse demonstrates comparable accuracy and, in some cases, superior quality when benchmarked against established software like RDKit, CONFORGE, ConfGenX, Torsional diffusion, and Conformator. We present an exhaustive ranking based on eight quantitative metrics and statistical analysis for robust conformer generation algorithms comparison and provide recommendations for their improvement based on our findings. We introduce the Cofactorv1 dataset, a complementary resource for conformer generator evaluation. Unlike traditional datasets with thousands of single-conformer molecules, the Cofactorv1 dataset features only seven small molecule cofactors but with hundreds to thousands of experimental conformers per molecule (sourced from the PDB). This diversity, encompassing 15-29 rotatable bonds, poses a significant challenge for conformer generation benchmarks. Cofactorv1 is a complementary dataset that serves as a valuable resource for developing and evaluating conformer generation methods like Moltiverse, pushing the boundaries of accuracy and diversity in this relevant field.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pena-munzenmayer_k-driven_2024,

title = {K+-Driven Cl−/HCO3− Exchange Mediated by Slc4a8 and Slc4a10},

author = {Gaspar Peña-Münzenmayer and Alvin T. George and Nuria Llontop and Yuliet Mazola and Natalia Apablaza and Carlos Spichiger and Sebastián Brauchi and José Sarmiento and Leandro Zúñiga and Wendy González and Marcelo A. Catalán},

url = {https://www.mdpi.com/1422-0067/25/8/4575},

doi = {10.3390/ijms25084575},

issn = {1422-0067},

year  = {2024},

date = {2024-04-01},

urldate = {2024-12-14},

journal = {International Journal of Molecular Sciences},

volume = {25},

number = {8},

pages = {4575},

abstract = {Slc4a genes encode various types of transporters, including Na+-HCO3− cotransporters, Cl−/HCO3− exchangers, or Na+-driven Cl−/HCO3− exchangers. Previous research has revealed that Slc4a9 (Ae4) functions as a Cl−/HCO3− exchanger, which can be driven by either Na+ or K+, prompting investigation into whether other Slc4a members facilitate cation-dependent anion transport. In the present study, we show that either Na+ or K+ drive Cl−/HCO3− exchanger activity in cells overexpressing Slc4a8 or Slc4a10. Further characterization of cation-driven Cl−/HCO3− exchange demonstrated that Slc4a8 and Slc4a10 also mediate Cl− and HCO3−-dependent K+ transport. Full-atom molecular dynamics simulation on the recently solved structure of Slc4a8 supports the coordination of K+ at the Na+ binding site in S1. Sequence analysis shows that the critical residues coordinating monovalent cations are conserved among mouse Slc4a8 and Slc4a10 proteins. Together, our results suggest that Slc4a8 and Slc4a10 might transport K+ in the same direction as HCO3− ions in a similar fashion to that described for Na+ transport in the rat Slc4a8 structure.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{arevalo_selective_2022,

title = {Selective TASK-1 Inhibitor with a Defined Structure–Activity Relationship Reduces Cancer Cell Proliferation and Viability},

author = {Bárbara Arévalo and Mauricio Bedoya and Aytug K. Kiper and Fernando Vergara and David Ramírez and Yuliet Mazola and Daniel Bustos and Rafael Zúñiga and Rocio Cikutovic and Angel Cayo and Susanne Rinné and M. Teresa Ramirez-Apan and Francisco V. Sepúlveda and Oscar Cerda and Eduardo López-Collazo and Niels Decher and Leandro Zúñiga and Margarita Gutierrez and Wendy González},

url = {https://pubs.acs.org/doi/10.1021/acs.jmedchem.1c00378},

doi = {10.1021/acs.jmedchem.1c00378},

issn = {0022-2623, 1520-4804},

year  = {2022},

date = {2022-11-01},

urldate = {2024-12-14},

journal = {Journal of Medicinal Chemistry},

volume = {65},

number = {22},

pages = {15014–15027},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zúñiga2022,

title = {A Direct Interaction between Cyclodextrins and TASK Channels Decreases the Leak Current in Cerebellar Granule Neurons},

author = {Rafael Zúñiga and Daniel Mancilla and Tamara Rojas-Rocco and Fernando Vergara and Wendy González and Marcelo A. Catalán and Leandro Zúñiga },

doi = {10.3390/biology11081097},

year  = {2022},

date = {2022-07-22},

urldate = {2022-07-22},

abstract = {Two pore domain potassium channels (K2P) are strongly expressed in the nervous system (CNS), where they play a central role in excitability. These channels give rise to background K+ currents, also known as IKSO (standing-outward potassium current). We detected the expression in primary cultured cerebellar granule neurons (CGNs) of TWIK-1 (K2P1), TASK-1 (K2P3), TASK-3 (K2P9), and TRESK (K2P18) channels by immunocytochemistry and their association with lipid rafts using the specific lipids raft markers flotillin-2 and caveolin-1. At the functional level, methyl-β-cyclodextrin (MβCD, 5 mM) reduced IKSO currents by ~40% in CGN cells. To dissect out this effect, we heterologously expressed the human TWIK-1, TASK-1, TASK-3, and TRESK channels in HEK-293 cells. MβCD directly blocked TASK-1 and TASK-3 channels and the covalently concatenated heterodimer TASK-1/TASK-3 currents. Conversely, MβCD did not affect TWIK-1- and TRESK-mediated K+ currents. On the other hand, the cholesterol-depleting agent filipin III did not affect TASK-1/TASK-3 channels. Together, the results suggest that neuronal background K+ channels are associated to lipid raft environments whilst the functional activity is independent of the cholesterol membrane organization.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{zuniga_direct_2022,

title = {A Direct Interaction between Cyclodextrins and TASK Channels Decreases the Leak Current in Cerebellar Granule Neurons},

author = {Rafael Zúñiga and Daniel Mancilla and Tamara Rojas-Rocco and Fernando Vergara and Wendy González and Marcelo A. Catalán and Leandro Zúñiga},

url = {http://dx.doi.org/10.3390/biology11081097},

doi = {10.3390/biology11081097},

issn = {2079-7737},

year  = {2022},

date = {2022-07-01},

urldate = {2022-07-01},

journal = {Biology},

volume = {11},

number = {8},

pages = {1097},

note = {Publisher: MDPI AG},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{mazola_common_2022,

title = {Common Structural Pattern for Flecainide Binding in Atrial-Selective Kv1.5 and Nav1.5 Channels: A Computational Approach},

author = {Yuliet Mazola and José C. E. Márquez Montesinos and David Ramírez and Leandro Zúñiga and Niels Decher and Ursula Ravens and Vladimir Yarov-Yarovoy and Wendy González},

url = {https://www.mdpi.com/1999-4923/14/7/1356},

doi = {10.3390/pharmaceutics14071356},

issn = {1999-4923},

year  = {2022},

date = {2022-06-01},

urldate = {2024-12-14},

journal = {Pharmaceutics},

volume = {14},

number = {7},

pages = {1356},

abstract = {Atrial fibrillation (AF) is the most common cardiac arrhythmia. Its treatment includes antiarrhythmic drugs (AADs) to modulate the function of cardiac ion channels. However, AADs have been limited by proarrhythmic effects, non-cardiovascular toxicities as well as often modest antiarrhythmic efficacy. Theoretical models showed that a combined blockade of Nav1.5 (and its current, INa) and Kv1.5 (and its current, IKur) ion channels yield a synergistic anti-arrhythmic effect without alterations in ventricles. We focused on Kv1.5 and Nav1.5 to search for structural similarities in their binding site (BS) for flecainide (a common blocker and widely prescribed AAD) as a first step for prospective rational multi-target directed ligand (MTDL) design strategies. We present a computational workflow for a flecainide BS comparison in a flecainide-Kv1.5 docking model and a solved structure of the flecainide-Nav1.5 complex. The workflow includes docking, molecular dynamics, BS characterization and pattern matching. We identified a common structural pattern in flecainide BS for these channels. The latter belongs to the central cavity and consists of a hydrophobic patch and a polar region, involving residues from the S6 helix and P-loop. Since the rational MTDL design for AF is still incipient, our findings could advance multi-target atrial-selective strategies for AF treatment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{González-Avendaño2021,

title = {PPI-MASS: An Interactive Web Server to Identify Protein-Protein Interactions From Mass Spectrometry-Based Proteomics Data},

author = {Mariela González-Avendaño and Simon Zuñiga-Almonacid and Ian Silva and Boris Lavanderos and Felipe Robinson and Roberto Rosales-Rojas and Fabio Durán-Verdugo and Wendy González and Mónica Cáceres and Oscar Cerda and Ariela Vergara-Jaque},

doi = {10.3389/fmolb.2021.701477},

year  = {2021},

date = {2021-06-30},

urldate = {2021-06-30},

abstract = {Mass spectrometry-based proteomics methods are widely used to identify and quantify protein complexes involved in diverse biological processes. Specifically, tandem mass spectrometry methods represent an accurate and sensitive strategy for identifying protein-protein interactions. However, most of these approaches provide only lists of peptide fragments associated with a target protein, without performing further analyses to discriminate physical or functional protein-protein interactions. Here, we present the PPI-MASS web server, which provides an interactive analytics platform to identify protein-protein interactions with pharmacological potential by filtering a large protein set according to different biological features. Starting from a list of proteins detected by MS-based methods, PPI-MASS integrates an automatized pipeline to obtain information of each protein from freely accessible databases. The collected data include protein sequence, functional and structural properties, associated pathologies and drugs, as well as location and expression in human tissues. Based on this information, users can manipulate different filters in the web platform to identify candidate proteins to establish physical contacts with a target protein. Thus, our server offers a simple but powerful tool to detect novel protein-protein interactions, avoiding tedious and time-consuming data postprocessing. To test the web server, we employed the interactome of the TRPM4 and TMPRSS11a proteins as a use case. From these data, protein-protein interactions were identified, which have been validated through biochemical and bioinformatic studies. Accordingly, our web platform provides a comprehensive and complementary tool for identifying protein-protein complexes assisting the future design of associated therapies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}