A machine learning-based virtual screening for natural compounds capable of inhibiting the HIV-1 integrase

نویسندگان

چکیده

HIV-1 integrase is an essential enzyme for the replication cycle, and currently, inhibitors are in first line of treatment many guidelines. Despite discovery new inhibitors, including a class molecules with different mechanisms action, resistance still relevant problem, adding options to therapeutic arsenal fight viral Sisyphean task. Because difficulty cost vitro screenings, machine learning-driven ligand-based virtual screenings alternative that can not only cut costs but also use valuable information about active compounds yet unknown action. In this work, we describe thorough model exploration hyperparameter tuning procedure dataset imbalance show several models capable distinguishing between or inactive against integrase. The best was then used screen natural product atlas compounds, resulting myriad share features known inhibitors. Here explore strengths shortcomings our discuss applicability domain guide differentiate “predictable” “unknown” regions chemical space.

برای دانلود باید عضویت طلایی داشته باشید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Evaluation of machine-learning methods for ligand-based virtual screening

Machine-learning methods can be used for virtual screening by analysing the structural characteristics of molecules of known (in)activity, and we here discuss the use of kernel discrimination and naive Bayesian classifier (NBC) methods for this purpose. We report a kernel method that allows the processing of molecules represented by binary, integer and real-valued descriptors, and show that it ...

متن کامل

Molecular docking based virtual screening of compounds for inhibiting sortase A in L.monocytogenes

Listeriosis is considered as an important public health issue. Sortase A (srtA) is an enzyme with catalytic role in L. monocytogenes that breaks the junction between threonine and glycine in the LPXTG motif (a key motif in internalin A (InlA) that plays an important role in listeriosis). Inactivation of srtA was shown to inhibit anchoring of the invasion protein InIA. This is in addition to inh...

متن کامل

Machine learning in virtual screening.

In this review, we highlight recent applications of machine learning to virtual screening, focusing on the use of supervised techniques to train statistical learning algorithms to prioritize databases of molecules as active against a particular protein target. Both ligand-based similarity searching and structure-based docking have benefited from machine learning algorithms, including naïve Baye...

متن کامل

Design of inhibitors of the HIV-1 integrase core domain using virtual screening

Acquired immunodeficiency syndrome (AIDS) is a disease of the human immune system caused by the human immunodeficiency virus (HIV). The integrase (IN) enzyme of HIV interacts with several cellular and viral proteins during the integration process. Thus, it represents an appropriate target for antiretroviral drugs (ARVs). We performed virtual screening of database compounds and designed analogue...

متن کامل

Inhibiting HIV-1 integrase by shifting its oligomerization equilibrium.

Proteins are involved in various equilibria that play a major role in their activity or regulation. The design of molecules that shift such equilibria is of great therapeutic potential. This fact was demonstrated in the cases of allosteric inhibitors, which shift the equilibrium between active and inactive (R and T) states, and chemical chaperones, which shift folding equilibrium of proteins. H...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

ژورنال

عنوان ژورنال: Frontiers in drug discovery

سال: 2022

ISSN: ['2674-0338']

DOI: https://doi.org/10.3389/fddsv.2022.954911