Druggable chemical space and enumerative combinatorics

Melvin J. Yu
June 2013
Journal of Cheminformatics;2013, Vol. 5 Issue 1, p1
Academic Journal
Background: There is a growing body of literature describing the properties of marketed drugs, the concept of drug-likeness and the vastness of chemical space. In that context, enumerative combinatorics with simple atomic components may be useful in the conception and design of structurally novel compounds for expanding and enhancing high-throughput screening (HTS) libraries. Results: A random combination of mono- and diatomic carbon, hydrogen, nitrogen, and oxygen containing components in the absence of molecular weight constraints but with the ability to form rings affords virtual compounds that fall in bulk physicochemical space typically associated with drugs, but whose ring assemblies fall in new or under-represented areas of chemical shape space. When compared against compounds in the ChEMBL_14, MDDR, Drug Bank and Dictionary of Natural Products, the percentage of virtual compounds with a Tanimoto index of 1.0 (ECFP_4) was found to be as high as 0.21. Depending on therapeutic target, this value may be in range of what might be expected from an experimental HTS campaign in terms of a true hit rate. Conclusion: Virtual compounds derived through enumerative combinatorics of simple atomic components have drug-like properties with ring assemblies that fall in new or under-represented areas of shape space. Structures derived in this manner could provide the starting point or inspiration for the design of structurally novel scaffolds in an unbiased fashion.


Related Articles

  • Divergence in physiological responses between cyanobacterial and lichen crusts to a gradient of simulated nitrogen deposition. Zhou, Xiaobing; Zhang, Yuanming; Yin, Benfeng // Plant & Soil;Feb2016, Vol. 399 Issue 1/2, p121 

    Background and aims: Nitrogen (N) deposition in arid lands is known to be increasing. However, N deposition gradients have unclear effects on physiological characteristics of biocrusts. This study tested if physiological characteristics are stimulated by low levels of N deposition and reduced by...

  • Theoretical predictions of the initial decomposition steps of dimethylnitramine. Velardez, Gustavo F.; Alavi, Saman; Thompson, Donald L. // Journal of Chemical Physics;8/15/2005, Vol. 123 Issue 7, p074310 

    The structures and energies of the reactants, products, and transition states of the initial steps in the gas-phase decomposition of dimethylnitramine (DMNA) have been determined by quantum chemical calculations at the B3LYP density-functional theory, MP2, and G2 levels. The pathways considered...

  • A new procedure for the spectrophotometric determination of nitrogen(II) oxide in solutions. Pukhovskaya, S.; Guseva, L.; Makarov, S.; Naidenko, E. // Journal of Analytical Chemistry;Jan2005, Vol. 60 Issue 1, p21 

    A new simple and reliable procedure was developed for the spectrophotometric determination of nitrogen(II) oxide. The procedure is based on the determination of excess oxygen after its reaction with NO. Alkaline solutions of thiourea dioxide were used for the determination of oxygen. It was...

  • Uptake of HO2 radicals onto Arizona test dust particles using an aerosol flow tube. Matthews, P. S. J.; Baeza-Romero, M. T.; Whalley, L. K.; Heard, D. E. // Atmospheric Chemistry & Physics;2014, Vol. 14 Issue 14, p7397 

    Uptake coefficients for HO2 radicals onto Arizona test dust (ATD) aerosols were measured at room temperature and atmospheric pressure using an aerosol flow tube and the sensitive fluorescence assay by gas expansion (FAGE) technique, enabling HO2 concentrations in the range 3-10 x 108 molecule...

  • Combined partial nitritation/Anammox system for treatment of digester supernatant. Gut, L.; Plaza, E.; Trela, J.; Hultman, B.; Bosander, J. // Water Science & Technology;2006, Vol. 53 Issue 12, p149 

    One-year (2004) comprehensive investigations in a semi-industrial pilot plant (5 m³) were carried Out with the aim of assessing the influence of operational parameters on the partial nitritation/Anammox system performance. In the system designed as a moving-bed biofilm reactor, the influent...

  • Oxygen and nitrogen abundances in cold H II regions from Sloan Digital Sky Survey. Zinchenko, I.; Pilyugin, L. // Kinematics & Physics of Celestial Bodies;Dec2011, Vol. 27 Issue 6, p273 

    Oxygen and nitrogen abundances for a selection of 113607 cold objects from the Sloan Digital Sky Survey (SDSS) spectra are derived. Values of oxygen abundances 12 + log(O/H) are obtained using three parametric N calibrations, one of which is constructed in this work. Values of nitrogen...

  • Using Rotational Raman Scattering to Study Gas Impurities. Boyarshinov, B. F.; Fedorov, S. Yu. // Journal of Applied Mechanics & Technical Physics;Sep2010, Vol. 51 Issue 5, p769 

    The use of optical diagnostic methods (spontaneous Raman scattering and coherent anti-Stokes light scattering) to measure gas impurity concentrations of less than 0. 1% is studied. The shapes of measured and calculated rotational Raman scattering spectra were compared to process experimental...

  • Studies of the Individual and Combined Effects of VUV Radiation and Hyperthermal O or Ar Atoms on FEP Teflon® and PMMA Surfaces. Jianming Zhang; Lindholm, Ned F.; Brunsvold, Amy L.; Upadhyaya, Hari P.; Minton, Timothy K. // AIP Conference Proceedings;1/5/2009, Vol. 1087 Issue 1, p154 

    Atomic oxygen and molecular nitrogen are the major constituents in the residual atmosphere at low Earth orbital altitudes, and they collide with spacecraft surfaces at relative velocities of ∼7.8 km s-1. The energy associated with these hyperthermal collisions is in excess of many bond...

  • Evaluation of Australian wheat genotypes for response to variable nitrogen application. Mahjourimajd, Saba; Kuchel, Haydn; Langridge, Peter; Okamoto, Mamoru // Plant & Soil;Feb2016, Vol. 399 Issue 1/2, p247 

    Aims: The key aim was to assess the genetic variation for nitrogen (N) response and stability in spring wheat germplasm to determine the scope for improvement of nitrogen use efficiency (NUE) under water-limited, low yielding conditions. A further aim was to evaluate NUE stability and...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics